Transcription: How to Create an Effective and Compliant Batch Record
The following transcription is taken from The Windshire Group’s webcast “How to Create an Effective and Compliant Batch Record Review Process Expert Panel Discussion”:
Terri Melvin: Welcome everyone to today’s webinar, How To Create an Effective and Compliant Batch Record Review Process Expert Panel Discussion. I’m Terri Melvin and I will be today’s moderator. We have with us today three expert panelists. The panelists will first tell us a little bit about themselves and then address some talking points in their particular areas of expertise. Then we dive into your questions live. I will now turn it over to our first panelist Dr. James Blackwell.
Dr. James Blackwell: Thanks Terri and thanks to everyone in our audience for joining us. I’m President and principal consultant for the Windshire Group. Our hope today is to make new industry friends and acquaintances and to serve as an information resource for organizations, by providing answers to some of your most pressing questions around this very important and timely topic. Just a couple of house rules before we get started. Please don’t ask anything that contains confidential information. Also for today’s webinar we are not offering any specific advice for anyone’s particular situation. We’re not responsible in any way for any use of the advice or opinions we express. After self-introductions, we will share a few of our personal thoughts about how to create an effective and compliant batch record review process and then we will get started with questions. I will then call our panel webinar with some concluding thoughts.
Prior to becoming a consultant, I held several senior technical positions within industry development and product companies. I have been an industry consultant for more than 12 years,assisting with CMC technical regulatory aspects for products and all major therapeutic classes at all stages of the product lifecycle. More recently, due to the growth in this area, we have done significantly more work in the quality system arena as well. Danielle has significant experience work in this area as well and I would like to now introduce Danielle DeLucy for her self-introduction.
Danielle DeLucy: I’m Danielle DeLucy. I am an independent consultant to pharmaceutical and biologics facilities. I have about now about 17 years’ experience dealing with quality systems, helping companies with Warning Letters, Consent Decrees and any type of quality system improvements that they may want to make. The core of my work has been done in the microbiology labs. I have a wealth of experience with microbiology, sterility assurance but late in my career I decided to branch off and really delve into the quality systems arena helping firms again with deviations, change controls, batch records and in fact relevant to this presentation today, I actually was head of a batch record review and release group for about five and a half years at a top biologics facility, so hopefully today you’ll bring away some important information and some tools and tips that we can help you with your batch record process and I believe our next presenter is Deborah Miller who has a lot of experience in this area as well. Deborah.
Deborah Miller: Thank You Danielle yeah at this point I’m saying over 30 years of experience in the field starting out in clinical laboratories and then during my tenure at the American Red Cross, I had five different positions culminating in the Director of Compliance when they were under their consent decree, which certainly gave me in-depth appreciation of the regulations in actually several regs to the pharmaceutical regs, the more specific blood regs and medical device, so I got a real in-depth experience there. I’ve been an independent consultant for 12 years helping companies move from quality theory to quality compliance and implementation of management systems and I’m looking forward to this webinar.
Terri: Thank you panelists and now Dr. Blackwell we’re going to go straight to your talking points
Dr. James Blackwell: Hold on I’m trying to pull up this session here
Terri : No problem, would you like me to go to another panelist and come back to you
Dr. James Blackwell: Sure go to Danielle and then we’ll step back to mine
Terri: Okay all right Danielle you are up
Danielle: Okay so today this is a very timely topic dealing with batch records review and format which I believe Deborah will get into, obviously we know that in our industry everything needs to be done right and done right the first time and that’s especially important when we’re talking about releasing the pharmaceutical and biological products to the market. Usually firms will have a specialized group of quality professionals called the batch review and release group and their purpose is to review the records, the executed records and once all the testing is in they also sign-off on the record and pretty much they’re the last people in the industry in that firm to actually see the data and the information before it goes out to the customer.
It’s a very important job, probably one of the most important jobs in the pharma and biologics arena and the quality group and it needs to be managed appropriately. We need to have effective and efficient management of that review process. There are a number of things that are looked at in batch record review. I actually, you know, have a specific webinar on this where we go through all of the different points to consider all the different parameters from critical process parameters to critical quality attributes to environmental monitoring, just to make sure that everything adheres to all the regulations and the compliance regs.
It’s important as well that we have all of the reviewers trained to the same standard. Many times firms will break the reviews down into an operations review and then that will go into the quality review and making sure that those two groups review to the same standard is paramount, you know, making sure that operations doesn’t do a quick cursory succinct review and think well the quality guys will take over and kind of catch what I miss. We really need to make sure that they are all reviewing, you know, as completely as they can.
QA and operations do have the opportunity to correct any errors or, you know, fix anything before it goes out the door. It is the time where we can look at our specifications and make sure that our product does meet all the specifications, and let’s face it, when we have this chance to do this we need to do it effectively and very well because we could potentially save our company thousands of dollars and fines and just, you know, having our integrity affected with a lot of the regulatory agencies if we release something that isn’t up to par. So with that those are my little points to consider for batch record review, hopefully Dr. Blackwell if you’re ready we can talk about your points to consider at this time.
Dr. James Blackwell: Thanks Danielle, so while there is a long- term trend in the industry to more electronic systems, paper records are going to be with many organizations for the foreseeable future. In many of these electronic batch records start as paper systems so it’s important to have well-designed batch records. This enables better batch record reviews and then it also makes a more efficient electronic batch record as well and we’ve seen this from some work in the past, so while released by exception electronic records eases this it doesn’t eliminate the need for batch record review in some form and having a well-designed batch record. So how does one achieve a well-designed batch record which we’ll review. Again as in many quality systems begin with the end in mind and so even if you’re revamping your systems you want to I recommend using information mapping principles and these are techniques to standardized batch record contents using standardize procedures for writers so that information is very easily processed by the people executing and by the people reviewing those records.
This really reduces the number of mistakes and when you reduce mistakes that also is going to feed into the batch record review process and greatly decrease the amount of effort in time that’s needed for that if you reduce those mistakes, and so it for me it starts with the KISS principle (keep it simple) and with a little help from Albert Einstein who’s that a model should be as simple as possible but not one bit simpler and so your batch record really is a model of your process, so you want to keep it simple, as simple as possible, but not one bit simpler.
Terri: Okay Deborah we’re going to move on to your talking points.
Deborah: Okay great, picking up from Dr. Blackwell’s information mapping the batch record end product is only as good as the design the actual design of the batch record. And this applies whether it’s a manual system or electronic system and we start off with the understanding and map the process and this is not just a high-level map, this is walking through the whole process and looking at all of the stops and starts along the production process and capturing those steps where you have already identified there are things to be considered, things to be concerned about, things to make sure that people are doing right because it can be done wrong, a very detailed map it doesn’t have to be formal, what it has to do is capture all the activities of the operators which takes me to my second point is to get the operators involved with the batch record. There are the ones that have to concurrently capture the information and you have to see what they’re doing when they’re supposed to be capturing the information, where their paperwork is, what else is going on and how your expectation of them capturing information coincides with the tasks that they’re performing.
And then of course we have the format, format, format. So many times I see batch records that are designed on a computer and printed out with little tiny spaces for people to record information in because the thought didn’t go into the fact that this was going to be converted from an electronic form into a manual form that has to be filled out, so please give the people enough space to record the information. Think about all of the fields that they may have to put N/A and see if there are areas where you can put an N/A checkbox instead of drawing lines, initialing and dating, standardize the forms as much as you can so that they can be confused but so that the same requirements are in each form are easy to see for the people recording the information and the people reviewing it. If you have units of measure or significant digits that aren’t going to change then pre fill those in and so they just have to fill the number in, again trying to set them up for success when they’re capturing information in the middle of manufacturing.
Observation versus verification; make sure in your SOPs and in your practice everybody understands what observation, observing a task and verification such as verifying the calculations mean. Recently, I worked with a company that required verification in their batch record but that required according to their SOP to observe the step and although people trained on the SOP they weren’t following that, so they were verifying it as a second check after the step was made which turned into a very big deviation. So use those terminologies appropriately and then make sure you implement them correctly. There was a Warning Letter a while ago from a company in another country where the FDA said that apparently the company didn’t understand the spirit of verification and observation because they had a step that had to be observed and they put the batch record in a vehicle and drove it to another facility to have the other person sign off on the observation which clearly wasn’t correct, so make sure that you use those words correctly and judiciously in your batch record. You may want to observe a weighing operation but you may also want to verify manual calculation.
Reference ranges, acceptance criteria, key information that can be over printed on the batch record form is very helpful. If you have the reference ranges there, the person recording the result has a baseline for them to understand whether the recording had a range result or not and the reviewers also will have a baseline on which to check the work, so those areas where you can put reference ranges, acceptance criteria and any other key information that are decision-making fields and the reviewer also has to catch, put them on the form. So review initials and signatures; throughout the batch record you will have people initialing tasks that they perform, look how you can group those and minimize the number of initials that they have to do throughout the form by consolidating tasks together if you can and review signatures. Make sure that it’s clear on the form what the review signature means. I’ve seen so many batch records where there’s a signature and I have no idea what that signature indicates, so either in your SOPs or in the batch record make sure that you know what that signature is.
The other thing I’d like to say about signatures is when I look at a batch record and I find errors and it has been reviewed and approved, my mind immediately goes to the QA reviewer who reviewed that batch record and missed it. I’m usually doing an audit and I’m flipping through a batch record for a short period of time on one audit day and if I’m finding obvious mistakes then I’m going to question the review process the reviewers training and the whole assessment and release of that batch, so just be mindful that the review function is very critical and when it gets past the reviewer to me that’s a big deviation. If they catch it fine, they can fix it, but when it gets past the reviewer then that puts the deviation in a whole different category and I think that covers the design of the batch record. Terri.
Terri: Excellent. Thank you to all the panelists for your points to consider, now we get to open it up for your questions, I encourage you while we have all these experts here simply type your questions into the question box. Now our goal today is to answer any and all questions live, however if we run out of time and don’t get to your questions for those that development and product companies will answer your question after the webinar concludes. Okay now for our first question, I think you hit something hot here on mapping. I think this is directed at Deborah but any of you can answer this; what tool do you use to map the process?
Deborah: Maybe Dr. Blackwell has more of an idea of a tool but from my point of view first step is to actually walk through the process. Don’t sit in a conference room and talk about the process. Walk through the process. You need to see not only what the steps are, which you’re capturing in batch record but you also want to see the actual physical facility and the setup and have your list of critical points and actually see how it’s being implemented. So when I say mapping yes we all understand information mapping and our little our boxes and our triangles and how one feeds into the other but more importantly to me when you’re talking about designing the batch record is to physically walk through with the people who are performing the tasks and actually get a gain an understanding of the process flow the true process flow as the product is being produced.
Dr. James Blackwell: Yeah I like thanks Deborah, I’d like to add on to that I think that question in terms of two flows and to be a little more specific I think it starts as a really good process flow diagram. You know as a chemical engineer that is so invaluable to an organization, so making sure you have captured all the appropriate critical and key information for your process there is a good place to start. In terms of a tool that then translates that into the batch record I think then you know anything really can work for that, whether it’s Excel or probably Word at that point is to translate an outline of the process. In terms of a business process for the actual batch record review process itself, if it’s just paper still you can have a business process that’s electronic that helps guide the organization to increase efficiency and then we have a proprietary tool, that helps companies who want to develop a more efficient process business process electronically.
Terri: Danielle do you have anything to add?
Danielle: Just on the process mapping to Deborah’s point I highly agree that walking through the process is very important because it comes to a point when you’re trying to train people to review the records it’s one of my pet peeves when I am in a facility and I see the batch record review training process and they’re sitting in their offices just looking at their records; you know, really getting out there and looking at the process carrying the batch record along with you really goes a long way, so I highly, you know, I certainly second what Deborah said about getting out there getting out into the floor and following that process along with the document in hand. It’s a great training mechanism and it’s very effective for those reviewers who are going to be reviewing those batch records at a later date.
Terri: Thank you I have another question here; is QA review required for every step of the process or only critical process parameters?
Danielle: I can touch on that a little bit as working as the head of a batch reviewed department for about five and a half years, our batch records were set up into sections to kind of help the format flow a little bit better. What we really recommended is that they didn’t have to review every single solitary step but there should be performed by and reviewed by steps in that in those sections for each of the different steps that occur and then QA would then either review that section but, you know, maybe it’s the set up section and the manufacturing section and then maybe the cleanup section you could do it that way or you can have them review the batch record, you know, from start to finish which obviously needs to be done per the regulations anyway. So I would say that they don’t need to, you know, review every step but usually that’s taken care of, you know, at the end when the executed batch record is sent to QA.
A lot of times firms will have quality shop floor coverage where there’s quality individuals that can certainly help sign off on those CPPs and CQAs, so that might be an option for you but certainly having a quality, you know, review maybe at each section would be something that I would recommend.
Terri: Anybody else like to chime in on that one?
Deborah: I would like to jump in here Terri. I set up some systems where the senior person, the team leader, the supervisor in the section as Danielle said the batch record might be set up into logical sections be responsible for that review for a couple of reasons; one when you’re responsible for that review and you’re part of the production I think you’re more alert to the content of the batch record and you’re not relying on somebody else checking your work. And secondly if you find something in real time you might be able to fix it without having a major deviation and so my encouragement is always to have a person involved in the production who is designated as a lead or a senior person do the review and be able to understand certain parameters, be able with concurrent objective evidence fix the problem before it gets moved on to the next section, so that’s kind of a vote for having the people in production doing that review. You know along you have your QA on the floor people to if it’s a large enough organization and that’s fine too but it’s that level of responsibility that you put on the production staff to do the review and catch these things that helps kind of encourage them to do a very thorough review.
Dr. James Blackwell: So the short answer is no it’s not just critical
Terri: Thank you for clearing that up. I think we have a follow up question here. You talked about senior people being there, we have a question here along that line; what is the best way to qualify a batch record reviewer?
Danielle: I’ll take that one. That’s actually one of my favorite things to talk about which is kind of weird but I’m definitely a quality nerd as you can tell but one of the how to qualify reviewer get that question a lot as a consultant as an independent consultant and actually was needed to defend this at one of the inspections that I was involved in. This isn’t, you know, any regulation it’s not something that, you know, someone said you must do but one thing that helped me in my department to kind of qualify the reviewer is, you know, I’ve been to many places and, you know, you shadow the person who’s trained, you know, you see what they’re looking at, you know, you talk back and front you know you see the different types of batch records many firms have, raw material batch records, API batch records, you know, filled product batch records, packaging batch records, so there’s a whole host of different types of templates that you can come in contact with, so you need to be trained on a lot of those. And so the thing that I like to, you know, kind of tell my clients and my colleagues is, you know, if you have a new person who, you know, it’s never reviewed a batch record, first where most is what we talked about a little bit ago, take them out into the shop floor get them very familiar with the process. I say this for all the quality professionals because they kind of do compliance behind the computer, you know, a lot of things are software related so you can review deviations, change controls documents, batch records kind of on your computer and you don’t ever get out there and take a look at the process. So get them out there, have them go walk through the process with the shop floor operator and then have them come back and have them take a blank batch record with them, one that’s not filled out and have them follow along the process again on the shop floor just so they could kind of match up the different processes with the batch record sections. We can then come back do the shadowing, you know, a few times with different templates and then what I like to do is to set up what I call a mock batch record and what we do is we fill it out with purposeful mistakes, so, you know, let’s say if it’s a 20 page or 10-page batch record I’m going to fill it up with about 10 to 15 purposeful mistakes.
Some are blatant like just basic GDP (Good Documentation Practice) issues, some are a little bit more difficult to find which would be, you know, somebody forgets to put in, you know, there might be blanks, there might be some critical processing parameter issues, there might be a kind of a crazy comment section that they need to address but they take the mock batch record test and then we give them a score at the end and if there’s 10 mistakes I say, you know, as one of my I guess our parameters they would need to at least find eight of those ten mistakes and score at 80% in order to be considered qualified. It was a way that we were able to show FDA and all the other different regulators that we had a documented process to show that these people actually can pick out the errors that may exist in a batch record. I’ve done it for years. I’ve passed it on to different firms who have adopted that and it really works very well and it’s a very robust training that they go through. We not only do it for quality but we also do it for our production reviewers as well. So that’s just an idea, something that, you know, I developed quite a long time ago that, you know, I’ve given to a lot of firms who seem to have really taken it on and even added to it, so I don’t know if Dr. Blackwell and Deborah have any other ideas but that’s something I like to do.
Deborah: I think that’s a pretty good process Danielle I would add to that, that after the person is considered to be trained and passed the test something that I initiated in my forensic testing lab stint is to have the person sit down with a knowledgeable senior quality person who’s very familiar with the whole batch record review process and ask them in some form, if you were going to train somebody on this reviewing this batch record what would you tell them, where would you tell them the important points are, where would you tell them the pitfalls are, can see if they can it’s not like a memory test they can have the batch record there and walk you through it, they can have the SOPs there if they want, the point is if they have a working conversational knowledge and can explain the importance of the sections and how they go about the review and what’s important when they’re reviewing then I have a pretty good idea that they really understood the training, they really understand the role and they understand the batch record review. So I turn the tables on them and say okay you’re teaching me walk me through it.
Dr. James Blackwell: Nothing from me Terri, those were great answers.
Terri: Okay great we have another question here; when designing a batch record do you have any input on determining the need for a step performer verifier as opposed to just a performer signature?
Dr. James Blackwell: I’ll start with that one, you know I think the ones that you want verified are ones that are critical to the process that you don’t have an independent means of verification whether it be an electronic system or data monitoring. You know a classic example is, you know, your formulation for your drug product and you’re adding, you know, specific ingredients with specific amounts, you know, those types of things for example you would want to witness and verify. Other things like calculations that aren’t critical to the process but you just want to ensure that they’re done correctly, those types of things can be verified types of steps. So I’ll turn over to Danielle and Deborah for their thoughts.
Deborah: I would go along with Dr. Blackwell and say that that’s part of your process mapping and the critical points that you have identified upfront and just reiterate that if it’s a step that’s going to throw off the next production processes, if you get it wrong of course you want a verification and if it’s something like weighing and the you may or may not have a hard copy capture of that weight, some weighing devices will give you a printout then of course you want observation, again if you’re barcoding the raw material in we’ve got a little a certain degree of certainty but if you’re not barcoding the raw material in when you’re weighing it then the observation point is important to make sure that they’re weighing the right raw material. And again when you set your processes up, you want to make sure that you only have one raw material in the mix at the time and you don’t have them all sitting on a table and just grab one, you want a linear process to minimize the chance of picking the wrong one.
Danielle: I don’t have anything
Terri: Okay great we have another question here; do you recommend using a batch review checklist and if so, what criteria do you look for in the checklist?
Danielle: I think a batch review checklist is a great idea; it’s a nice tool to use especially if you want to make sure that the reviews are consistent. A batch review checklist for me would really just include kind of making sure that all the CPPs and CQA were looked at, we have a reminder about good documentation practices, we’d make sure that there were, you know, no empty spaces, that the units were consistent and significant figures were consistent throughout, that there was a signature page people were trained, you know, and he got any of the different printouts maybe autoclaves printouts or if you had any other type of automated machinery that was used that a tape that they were attached, so all those different things I would definitely include on a batch review checklist. Just make sure that it is part of your standard operating procedure that you would be using one of these and make sure that it is an official form that’s linked to your quality approved standard operating procedure if you’re going to use one of those.
Deborah: And I would just I concur that a checklist when designed well is a help, you don’t want to have a lot of business in there with items that are understood that are being checked but I would also say make sure it matches the process flow that you did at the beginning of designing this batch record. You don’t want your checklist to have additional things that aren’t in the process flow or vice versa.
Terri: Okay great. I think we answered that question, we have another question; is it important to document all deviations on the batch record itself or can deviations found during the review process be noted on a checklist, back to the checklist?
Danielle: In my opinion I would think that all deviations should be noted in the batch record; that’s been my preference as a batch review person and a quality deviation reviewer, this is just so that it’s documented, you know, if that executed batch record was pulled for review during an inspection you definitely want to at least annotate, you know, the deviation number where you found it, so if there are any deviations either found during the manufacturing process or the review process I would certainly list them in the actual batch record as to where they were found. You could also do it in the checklist but certainly at least put it in the batch record in my opinion.
Deborah: I agree that the deviation needs to be referenced as close to where it occurred in the production process, in the batch record. Recently had a batch record and one page was a nightmare of GDP errors, it had I don’t know eight or more GDP errors and it was like a Rube Goldberg of trying to follow, these errors and the corrections and then the errors and the corrections and the company actually reconstructed that page but they only linked it one way. So the new page said this is a reconstruction of the previous page but the page with all the errors did not link back, so it looked like they had all of these GDP error Corrections that didn’t end up well stand alone and the only reason that I knew that there was a second page which had already been was previous to this one was because the QA people told me, so that was kind of a nightmare but if you have to reference, if you have to reconstruct another page for whatever reason it could be that it just got wet make sure that they’re linked both ways.
Dr. James Blackwell: Yeah I definitely agree that deviations that happened during execution of a batch record need to be captured in the batch record and noted and I’ve seen varying practices in terms of what deviations associated with that production batch are also captured in the batch record but what Danielle said it is a good practice. It also helps ensure that as part of batch release that you’ve made sure that you’ve reviewed and satisfied all those investigations before batch release.
Terri: Okay Danielle I think this next one you’re going to love; what if any differences are there between GLP and GMP batch records?
Danielle: That’s a good question. My background is in steriles and injectables, so I’ve been with GMPs for almost all of my career so I’m extremely conservative when it comes to a batch record design and batch record review because of my background but pretty much I believe that they’re pretty much the same with GLP and GMP if you’re going to be, you know, looking at the manufacturer of, you know, of different products, you certainly want to capture the same thing regardless of, you know, what industry that you’re in and you want to make sure that good documentation practices are followed for each, you may not have critical practicing parameters or critical quality attributes per say but I would say they’re pretty much the same in my opinion. I don’t know about Dr. Blackwell or Deborah you may have a little bit more experience in the other realms that you can offer some suggestions.
Deborah: I would just say that with GLP records sometimes there are lab books or equipment manuals that are related to the test analysis and they need to be referenced in the record. I’ve had places that for the GLP record, they assumed that if they put the instrument that they use that you know where the information is because that instrument may have its own book but it needs to be all of those links between the equipment and the conduct of the tests need to be direct and solid so that there are no gaps in the batch record or the analysis record for what was used and all of the important information about the equipment and the standards and all of the other items that go into that analysis. And sometimes I see that the GLP records assume that you know where to find the information that’s not in the record.
Dr. James Blackwell: And those should be reviewed as well.
Deborah: Right oh yes sorry thank you.
Terri: Okay excellent here’s another question about reviewing; what are some suggestions for speeding up the review cycle time and disposition process?
Deborah: Speed up is kind of not in quality’s vocabulary
Dr. James Blackwell: I think it is I actually and I spoke to this at the beginning, I think that we design processes well whether it’s a business or an actual process, a simpler process is one that’s faster and has higher quality. So it begins with the points that I spoke to at the beginning, develop a well-designed system, make it simple, make it effective and when you do that that’s going to reduce mistakes and that’s going to speed up your reviews.
Deborah: Okay given in that context I would concur and I would say don’t put anymore reviews and sign offs in the batch record than you actually need, so this goes back to his point about the design of the batch record. You cannot ever have enough checks to check the checkers. In my experience in the forensic lab the one time that we had a wrong result go out was when somebody said well I knew so-and-so was going to check it and she’s really good and she catches everything. So be very mindful of the human factor in having too many checks on people because they’re all diluted as far as the import that is given when the reviewer is doing it, so you don’t need a lot of checks if you don’t need them.
Dr. James Blackwell: That’s a great point Deborah. More compliance doesn’t equate to more quality and people make that mistake and start going down that rabbit hole. Again, make sure you design your process you only have the review and oversight that is necessary and again focus on those areas that are of most risk and importance that makes ensures you’re using your resources efficiently; to make sure they’re focused on the important things which improves the overall quality of your product.
Terri: Ok we have a specific question here; during issuance of the batch record, do you need to initial date each page of the batch record?
Danielle: In my experience we usually firms can set up a verification and review process when you’re issuing the batch record where, you know, that’s kind of I guess you can if you want but if you have a process to say that you’ve printed the batch record you’ve certified it and then you sign off that it has been certified, it’s not necessary to initial each page. Some of the firms that I’ve worked with have put that right on the title page that it was printed on this date by this person and certified on, you know, this date by this person and that kind of covers it but if, you know, you could certainly do that I really think it’s a necessary requirement though but I’ll leave that open to Deborah and Dr. Blackwell.
Dr. James Blackwell: It’s certainly a common practice. I guess I’ll defer to you and Deborah whether it’s necessary or not.
Danielle: Just to be clear we’re talking about initially the blank each page.
Dr. James Blackwell: I interpreted the question is that page has been reviewed.
Deborah: Okay I think we’ve got two different scenarios going here as far as printing the blank batch record is I would go with Danielle and how you define that and as you say you can put it on the first page that it was printed on this day and it’s inclusive of pages one through seventy three. As far as reviewing each page, as long as the pages are concurrent, I would think that the initials would be related to the section not necessarily the page, I’m not sure what the initials are supporting on each page as a clarification
Terri: Not yet I think we’ve answered the question.
Deborah: I mean, in general, we know there’s no reg that defines that level of detail, I mean the important thing is that you define what your goal is by having that requirement. If you don’t have any problems with having deviations on pages or missing pages or anything that not initially could lead to then the question is why are you doing it? It wouldn’t impress me as a reviewer.
Terri: Great. The person who asked the question said thank you, so I believe you answered the question. Here’s a different one; when it comes to the KISS, (kiss principle) what level of detail instruction should the batch record capture versus the related processing SOPs?
Dr. James Blackwell: Yeah again that’s a great question and I definitely have seen different practices on that. It often comes down to, you know, an operator perspective on this as well so that it’s clear to them, so you often see those specific SOPs broken out where it’s sort of a standalone body of work that where you don’t need to record a lot of the specific information on that process but it’s more of an instruction set. So I think that’s the most common way I’ve seen that broken out, so think of it that way and so then the batch record would be more about okay this part of the process we did execute this procedure and then we’re going to document any data or in verification that was executed versus those SOPs. So this is one way to keep your batch record simpler but again I would think of it in terms of what data needs to be recorded and documented and what can be broken out as a specific instruction set, I’m open to other thoughts from Danielle and Deborah on that.
Terri: Okay Danielle had to jump off but Deborah do you have anything to add.
Deborah: I do. It is kind of two-edged sword I guess. You don’t want to have too many instructions in the batch record I don’t think. I would go with the process defined in the work instruction or the SOP. However there may be a step where they cannot do the concurrent documentation just because of the nature of what they’re doing in the task and there may be either in the SOP or on the batch record, a statement that relates to how you handle that like, you know, record as soon as or record before the next step to just make sure that everybody understands that it’s not exactly concurrent because of the nature of the task. That may be a unique situation that you want to have on the batch record. I’m not saying you have to have it but that’s an example of something that would be kind of a very specific instruction just for that step.
Terri: Okay thank you, what should a manufacturing review consist of?
Deborah: What should a manufacturing…
Dr. James Blackwell: Yeah I’m not sure I understand that question Terri
Terri: Yeah. That is as it was written, can you clarify?
Dr. James Blackwell: While they’re doing that do we have another question we can jump to?
Terri: We do and here we go; what about P and IDE review?
Deborah: I would guess that’s part of your process flow, I’m not sure that is part of executed batch record review. Dr. Blackwell?
Dr. James Blackwell: Yeah I’ve never seen that part of a batch record review, that’s more, you know, foundational to your quality, you know, system or change control or something like that so you know once that has been generated then you know that becomes a part of your change control process.
Terri: Okay I have clarification from that other question we had, what they want to know is what’s the difference between a manufacturing review versus a QA’s review?
Dr. James Blackwell: Yeah well manufacturer is responsible for, you know, executing the process the instruction sets, so their review is to verify that they have, you know, executed it correctly. The QA review is more that it’s a review of manufacturing has executed the record as they are supposed to execute it, so this gets back a little bit to some of the previous discussion about well, you know, how much detail should the QA be reviewing, obviously they can’t go and review and verify every bit of information, so it’s a little bit of layered where they’re more responsible I guess you could say and ensuring that manufacturing has done their job correctly and so it’s more of Manufacturing’s job to check, you know, the steps are executed correctly and that their proper information was recorded, you know, at the time of execution and the reviews within manufacturing is usually at the supervisor level and again it’s that first check that they’ve done their job correctly.
Deborah: And I would just say I agree and I would add on to that, when we talked about training reviewers I think we only touched on QA training but the training of the manufacturing reviewers is very important because those are the people that are real-time reviewing this record and they have the capacity to catch and possibly fix to correct deviations instead of having to have it be a correction later on. You know one of the significant differences is QA is after the fact and so any deviation that’s found is going to have escalated just by the movement of time.
Dr. James Blackwell: That’s a superb point Deborah, yes and I would reframe it slightly is that it’s an opportunity for manufacturing to catch a mistake before it becomes a deviation.
Deborah: Exactly, exactly and so the training of those people it’s critical to make sure that they understand they’re not just signing their initials that they were present. They’re actually reviewing and ensuring doing the first check to catch those mistakes.
Terri: I have a very specific question here; should calibration times be noted on the batch record?
Dr. James Blackwell: I think the key there is QA should. I don’t think it has to. I have seen that practice, I think it might come down to the criticality of that step and if it’s an area that’s been problematical in the past but I certainly don’t think that’s a requirement. Any thoughts on that Deborah?
Deborah: Yeah I know I would never make that a requirement either, the process of linking the equipment that was calibrated to the batch record is clearly very important. If we’re talking about a laboratory analysis record, we might be talking about a different kind of calibration, so we have to be careful on what we use the word calibration for but in general I would never make that a should or a shall.
Dr. James Blackwell: I agree
Terri: Okay Dr. Blackwell this one’s for you. I think someone’s familiar with Stabilityshire; they’re asking how is Stabilityshire integrated into a batch review?
Dr. James Blackwell: Well yeah it’s not part of the batch review process. This is a service where we have validated software specific to stability data, so it’ll actually do the statistical analysis around that and we can produce a compliant report to that, so it’s not specific to a batch record.
Terri: Okay then they want to know how do we deploy Process Pad in a batch review?
Dr. James Blackwell: Yeah well that’s a great question and I speak generically for any you know continued verification software not just ProcessPad, in that the important thing is that, you know, it depends on different levels, most people are using this for a trend analysis and investigations and process improvements. So to the extent that you take software like that that’s validated, people are now taking that concept to a point where you’re generating as I mentioned at the beginning, you know, exceptions and producing exception reports, so people have used Process Pad to validate it and produce an exception report and then use that exception report to aid, and in essence, speed up the batch record review process.
Terri: Okay I think we have time for maybe one more question; how do you handle instruments that are not out of spec but have enough offset to invalidate results?
Deborah: That’s kind of a qualifying question. You have to do your trend analysis on your instrument performance, I just worked with a company on this and have in your SOP how you’re going to manage out of trend which I think they’re talking about as opposed to out of spec and it really depends on the analysis and the impact to the manufacturing process for that analysis, but in general, you can’t just start off with this is not out of spec but it’s out of trend unless you’ve done the homework and figured out what your trends are and then you know once you’ve defined that and you put that in your SOP as far as how you’re going to handle a lot of trend and what you’re going to do about the sample and the potential for retesting and I say that very cautiously then you can handle the instrument performance.
Terri: I think we want to answer this last question; how do we store paper batch record reviews?
Dr. James Blackwell: Well I guess the short answer it’s just you should have, you know, a record archiving process and procedures around that, so generally most organizations will keep ones that have been executed, you know, on site, you know, for a couple years or so and then, you know, Deborah may have more insight into this and then do long-term storage off-site.
Deborah: Well I think the basic thing is to store the review with the record, not separate from it because I think the question was how do we store the review? If you’re for some reason need the review for another reason, then you would have to have a certified copy of it but definitely the review needs to go with the record.
Dr. James Blackwell: And then follow your documentation practices
Deborah: And your archiving depends on how quickly you can retrieve it because if you have to be able to retrieve it relatively quickly, so then you define, you know, what that is and which goes into the whole shelf life of the product and all of the other things associated with record-keeping.
Terri: Well we respect everyone’s time and it’s almost 12 o’clock, so Dr. Blackwell do you have some closing remarks or ?
Dr. James Blackwell: Yes. Thanks everyone for attending. We hope you came away today with some useful insights and a greater understanding of batch records. If anyone has any specific consulting needs on this or another topic please reach out using our contact information on the site. We’d love to hear from you. We look forward to sharing our expertise with you in the future. Bye everyone.
Terri: Bye everyone, have a great day.
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