InstantGMP Compliance Series - Improving Batch Production Records


Published on

Batch record violations were frequently cited during FDA inspections of dietary supplement manufacturers. This presentation provides some guidance on what is needed for batch records to be in compliance with GMPs.

  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide
  • Welcome to the InstantGMP compliance Series for Dietary Supplements on how to improve Batch Production Records. The quality and manufacturing experts at InstantGMP prepared this GMP Compliance Series of presentations to review good manufacturing practices and cGMP compliance for dietary supplements manufacturing. Our experts hope these presentations will help you avoid any cGMP compliance issues in your facility. A common reasons for the FDA to issue Warning Letters to Dietary Supplement companies was due to poorly executed batch records. This presentation describes how to improve batch production record procedures.
  • Many of the common problems found by FDA inspectors of dietary supplement manufacturers center on incomplete batch records. The FDA expects to see details on how firms record the production of their products and how they make decisions when changes are made during the production process. Firms are required to make and keep written procedures for specifications, Quality Control operations, Master Manufacturing Records, returned goods and equipment. The FDA often cited manufacturers for failing to provide written documentation that specifications were set and that testing was completed before using a component or ingredient in a batch. In many cases, there were no written master manufacturing records (MMR) for each unique formulation of dietary supplements or the batch production records did not follow the Master Manufacturing Record. The FDA expects documentation to show that batches were properly made and that the quality control personnel performed their review and disposition of products at the time of manufacturing.
  • Batch production records are needed to document when each batch was produced, what lots of raw materials and dietary ingredients were used in that batch and that the product was made in compliance with the master manufacturing formula. The record must show that any deviations that occurred during manufacturing were investigated and resolved. These requirements will allow uniform batches that meet established quality requirements and specifications. If a problem occurs or a customer complaint is received after the batch gets to the market, the batch records can then be reviewed to assess the issue. A good batch record system keeps track of raw materials and ingredients that went into a batch and makes it easy to find a root cause, which can prevent the problem from happening again.
  • The basics of cGMP manufacturing are actually pretty straight forward. Manufacturing instructions and procedures have to be clear and unambiguous. The manufacturing processes needs to be clearly defined and have controls at each critical step of the process. Manufacturing facilities must be designed to minimize cross-contamination and mix-ups. Operators have to be trained and their training must be documented. Records have to demonstrate that all required steps were taken and that any deviations to the written process were investigated by the QC unit and resolved before the batch was dispositioned.
  • Definitions are useful in understanding how good batch records can be constructed. A component is any substance used in the manufacture of a dietary supplement, including substance that may not appear in the finished batch. An ingredient means any component used in manufacturing that will be in the finished batch. Ingredient includes dietary ingredients and raw materials. In-process material means any material that is processed before becoming part of the batch.
  • Batch means a specific quantity of a dietary supplement that is uniform, that is intended to meet specifications for identity, purity, strength and composition, and that is produced during a specified time period according to a single manufacturing record during the same cycle of manufacture. Batch number, lot number, or control number means any distinctive group of letters, numbers, or symbols, or any combination of them, which will allow the complete history of the manufacturing, packaging, labeling, and/or holding of a batch to be determined.
  • Theoretical yield means the quantity that would be produced at any appropriate step of manufacture or packaging of a particular dietary supplement, based upon the quantity of components or packaging to be used, in the absence of any loss or error in actual production. Actual Yield is the total quantity of product measured at the end of manufacturing a batch. The Percent Yield is calculated by dividing the Actual Yield by the Theoretical Yield and multiplying by 100. The Percent Loss is 100 minus the Percent Yield.
  • In order to comply with the cGMP requirements, a Master Manufacturing Record for manufacturing, packaging or labeling must be prepared and followed. There has to be one master manufacturing record for each unique formulation of a dietary supplement product and batch size. This will allow you to ensure uniformity in the finished product from batch to batch.
  • Each “batch production record'' or “batch record'‘ has to follow its corresponding Master Manufacturing Record. cGMPs require that an appropriate batch production record be followed the every time a batch of a dietary supplement is manufactured. The batch production record must include complete information for the production and control of each batch. What Must the Batch Record Include? A batch, lot, or control number must be set as a unique identifier of each batch. Each component has to have a unique identifier and the weight or measure that was added to the batch. Each piece of equipment and each processing line used in producing the batch has to be identified and the batch production record has to include the date and time of the maintenance, cleaning, and sanitizing of those equipment and processing lines, or a cross-reference to their records where that information is kept. The batch record has to include a statement of the actual yield and a statement of the percentage of theoretical yield at each appropriate phase of processing.
  • In-Process controls includes monitoring the steps where control is necessary to ensure the quality of the finished batch. Each firm must determine if in-process specifications are met and detect any deviation or unanticipated occurrences. A COA from a qualified vendor can be included in the batch to verify information except for the identity of a dietary ingredient. You will need a scientifically valid method for each specification for which testing or examination is required.
  • Batch production record must also include the actual results obtained during any monitoring operation. These can be written into the batch record or a cross-reference to where the data are stored can be provided. If an outside laboratory performed the testing, a copy of the test results or a cross-reference must be included in the batch record. The batch production record must include an actual or representative label, or a cross-reference to the location of the actual or representative label. There must be documentation that quality control personnel reviewed the batch production record; approved or rejected any reprocessing or repackaging and dispositioned the batch.
  • A deviation can be an unanticipated event that occurs during production and could possibly result in adulteration of a component of a dietary supplement. Pre-planned deviations from the BPR may be written and approved as well. Deviations should be noted in the batch production record along with documentation that describes either the reasoning for the planned deviation or the investigation into the root cause of an unplanned event. Actions taken to correct the deviation and prevent a recurrence of the deviation must be identified. This information should be recorded in a Corrective Action and Preventable Action Register so trends can be identified and a record of resolution programs can be kept. The quality control unit will need to evaluate whether or not the deviation resulted in or could lead to adulteration of a component, dietary supplement, packaging, or label to ensure the quality of the product. A batch cannot be reprocessed or approved for distribution without QAU approval of a scientifically sound plan for acceptable in-process adjustments. Regulations prohibit the use of rejected ingredients unless the quality control unit determines that in-process adjustments are possible to correct the deviations or occurrence. Others may assist quality control personnel in gathering and considering information relevant to the review and decision, but Quality control personnel must approve or reject all processes, written procedures, controls, tests and examinations, and deviations.  
  • The review of the batch record must be done by the quality unit. This includes the review of records such as receiving records and determining whether each finished batch conforms to product specifications. The reviewer has to assure that no contamination occurred and that all manufacturing deviations were resolved.
  • The final rule describes how a production and process control system has to be set up because only end product testing can ensure the quality of the final product. The first step is to use high quality components that meet well-defined specifications. The confirmation of the identity and other quality attributes of each component that will be used in manufacturing is required. In-process controls and specifications should be established for every step that is critical for the quality of the final product. Testing for potential contaminants should be conducted to prevent the batch from becoming adulterated. Every batch should be tested unless there is a well defined sampling and testing program in place that works in conjunction with GMPs. Make sure that any necessary tests or examinations are completed and recorded and then reviewed by Quality Control before the dietary supplement is released for distribution.
  • QC and or production personnel must monitor the in-process points, steps, or stages where control is necessary to ensure the quality of the finished batch Perform in-process checks like capsule weights or tablet hardness and determine if the in-process specifications are not met. If not, record a deviation or any unanticipated occurrences. Quality personnel must conduct deviation investigations make the disposition decisions. Meeting in-process specifications will help ensure that the final product specifications are met and that the product produced has the correct identity, purity, strength, and composition.
  • Specifications must be established for any point where control in the manufacturing process ensures quality, for example, heating or cooling steps. If it is critical that a certain piece of equipment be cleaned and/or sanitized after handling certain raw materials to ensure that there is no microbial contamination, then specifications have to be set and met. If the manufacturer fails to establish a specification for cleaning and/or sanitizing after handling those raw materials, the product could become adulterated. Limits must be established for points where cross-contamination may adulterate the batch or where environmental hygiene is necessary to prevent adulteration of the finished batch.
  • The retention period for controlled records should correlate with the length of time that product complaints are likely to arise related to the manufacture of a dietary supplement. Such correlation will increase the likelihood that, if a problem with a dietary supplement is identified that may be associated with a violation of CGMP, the manufacturer can address the issue with proof in hand. The packaging date or “date of manufacture” does not necessarily indicate the availability of the dietary supplement product in the marketplace, it has no effect on the amount of time records must be kept. It is possible that such product could be held for a period of time after manufacture before entry into the marketplace and possible consumer consumption. A more accurate time period is calculated by the date of distribution. The final rule now requires a record retention period of 2 years beyond the date of distribution of the last batch of dietary supplements associated with those records, or 1 year past the expiration date.
  • Records are an indispensable component of cGMP. The FDA must be able to inspect your Master Manufacturing Records and other supporting documentation during their inspections. The records required by this final rule provide the foundation for the planning, control, and improvement processes that constitute a quality control system. Implementation of these processes in a manufacturing operation serves as the backbone to CGMP. if you use reduction techniques, such as microfilming, you must make suitable reader and photocopying equipment readily available to them. If you use electronic manufacturing or documentation systems, these must meet 21 CFR Part 11 requirements for Electronic Documentation and Electronic Signature.
  • This is a sample electronic batch production record screen where the instructions to the operator are displayed and fields are available to record results, comments or deviations.
  • There are many reasons that companies will want to adopt an electronic manufacturing system. They are more efficient than manual systems. For example, they can shrink or eliminate the redundant process and forms that occur in manual systems. They can trim time and costs compared to manually compiling and reviewing documentation. They can reduce errors, omissions and deviations.   Probably the most important advantage is that a transition to an electronic system can provide opportunities to reorganize and to update processes to make the whole plant work better. All of these benefits taken together will result in increased throughput, quality and margins.
  • Our goal at InstantGMP™ is to make cGMP compliance easy. InstantGMP is a complete Electronic cGMP Manufacturing Execution System for dietary supplements and pharmaceutical products. It seamlessly incorporates everything necessary for cGMP manufacturing in one database. It is a web-based application makes all data visible to everyone on demand. It is unique in that it uses built-in quality procedures to make cGMP compliance more manageable. It is a complete solution that provides opportunities for greater flexibility, visibility and productivity in your operation.
  • This presentation is just one of many articles and videos available on cGMP compliance for Dietary Supplements. You can find the rest at the Resource Center at
  • InstantGMP Compliance Series - Improving Batch Production Records

    1. 1. InstantGMP Compliance Series for Dietary SupplementsImproving Batch Production Records
    2. 2. Problems with Batch Records• Lack of detail on procedures• Inadequate information on decisions for changes during production• Failure to show specifications and test results• No Master Manufacturing Records• Batch records did not follow the Master• QC did not properly disposition batch Electronic cGMP Manufacturing Execution System
    3. 3. Why Batch Records are Important• Shows when product was produced• Documents• Assures consistency in how processes are followed• Enforces uniformity and quality• if adulteration occurs, records will show the source of the material so that its use can be stopped Electronic cGMP Manufacturing Execution System
    4. 4. Basics of cGMP Manufacturing• Instructions and procedures are clear and unambiguous• Manufacturing processes are clearly defined and controlled• Facilities designed to minimize cross- contamination and mix-ups• Operators are trained• Records demonstrate that all required steps were taken• Deviations investigated and resolved Electronic cGMP Manufacturing Execution System
    5. 5. Definitions• Component – Any substance used in manufacturing – Some may not appear in finished batch• Ingredient – Any component that becomes part of the finished batch – E.g. dietary ingredient or raw material• In-Process Material – Any material that undergoes its own process before becoming part of the final product Electronic cGMP Manufacturing Execution System 5
    6. 6. Definitions• Batch – Specific quantity of a product that is uniform – Intended to meet full set of specifications – Made on a single batch production record during one manufacturing cycle• Batch Number – Lot or control number which refers to complete manufacturing history of batch Electronic cGMP Manufacturing Execution System
    7. 7. Definitions• Theoretical Yield – Quantity of product to be made• Actual Yield – Total quantity of product measured at the end of manufacturing a batch• Percent Yield – Actual Yield / Theoretical Yield X 100• Percent Loss – 100 – Percent Yield Electronic cGMP Manufacturing Execution System
    8. 8. Master Manufacturing Record• Must prepare and follow a ``master manufacturing record for: – Manufacturing – Packaging – Labeling• One MMR for each unique formulation and each batch size• Ensures uniformity in the finished product from batch to batch Electronic cGMP Manufacturing Execution System
    9. 9. Batch Production Record• Must have a new batch record for each new batch• Include: – Unique identifier for each batch – Identity and weight of each component – Identity of equipment and processing lines – Date and time of equipment maintenance and cleaning – Statement of actual and % theoretical yield Electronic cGMP Manufacturing Execution System
    10. 10. In-Process Controls• Must monitor the steps where control is necessary to ensure quality• Determine whether the in-process specifications are met• Controls include COA from qualified vendors• Dietary ingredients need identity testing• Use scientifically valid method for each specification Electronic cGMP Manufacturing Execution System
    11. 11. Batch Production Records• Also include: – All results obtained during the operation – For tablets and capsules – add steps to prevent metal or foreign materials from equipment from getting into the batch – Reference to location of the label – Proof that quality control reviewed the BPR and dispositioned the batch Electronic cGMP Manufacturing Execution System
    12. 12. Deviations• Triggered by any unanticipated occurrence could result in adulteration• May not reprocess a batch that deviates unless approved by Quality• Quality must conduct a material review• Then make a disposition decision• Corrective and Preventative Actions (CAPA) needed for deviations Electronic cGMP Manufacturing Execution System
    13. 13. Batch Record Review• Quality personnel must conduct all reviews and make disposition decisions• Review receiving records• Determine if all specs are met• Make sure no contamination occurred• Resolve all manufacturing deviations Electronic cGMP Manufacturing Execution System
    14. 14. Production Controls• Cannot use only end-product testing to ensure quality• Start with high quality components that meet well defined specifications• Confirm the identity of each component• Detect problems through in-process controls and specs• Prevent contaminates from entering the batch• Test every batch unless a sampling and testing program is combined with good controls• Quality Control reviews all documentation Electronic cGMP Manufacturing Execution System
    15. 15. In-Process Controls• Monitor the steps where control is necessary to ensure quality• Perform in-process checks like capsule weights or tablet hardness• Determine whether the in-process specifications are met - If not, record a deviation• Meeting in-process specs helps ensure final product will meet requirements Electronic cGMP Manufacturing Execution System
    16. 16. Control Point Specifications• Needed for any point where control in the manufacturing process ensures quality, for example: – Heating steps – Cooling steps – Specific sanitation procedures to protect product – Points where cross-contamination might occur – Where environmental hygiene is necessary Electronic cGMP Manufacturing Execution System
    17. 17. How Long Must Master Records be Kept?• Length of time product complaints are likely to arise• Generally 2 years after date of distribution (not date of manufacture)• If shelf life dating is used, 1 year past the shelf life date• Packagers and labelers that return the product to the manufacturer for distribution do not need separate records Electronic cGMP Manufacturing Execution System
    18. 18. How Must Master Records be Kept?• Records are the backbone of a quality system• FDA must have the means to examine them during an inspection• If microfilming is used, a suitable reader must be available• If electronic, must meet 21 CFR Part 11 requirements Electronic cGMP Manufacturing Execution System
    19. 19. Batch Production Record –Manufacturing Instructions
    20. 20. Benefits of Electronic Manufacturing• More efficient than manual systems• Shrink or eliminate redundant processes and forms• Trim time and overhead costs• Reduce errors, omissions and deviations• Provide opportunities to reorganize and update processes• Increases throughput, quality and margins Electronic cGMP Manufacturing Execution System
    21. 21. InstantGMP™• Electronic cGMP Manufacturing Execution System• Seamlessly incorporates everything necessary for cGMP manufacturing in one place• Web-based application makes all data visible to everyone at all times• Uses built-in quality procedures to make cGMP compliance easy• Provides opportunities for more flexibility, visibility and productivity Electronic cGMP Manufacturing Execution System
    22. 22. InstantGMP™Find more presentations and videos on cGMPManufacturing and Dietary Supplements in the Resource Center at