Discover the significance of master production and control records in ensuring cGMP compliance in pharmaceuticals. Learn about key components, documentation practices, and training requirements to maintain product consistency and quality assurance.
From the exhaustive range of cGMP guidelines, one section has a greater significance in our quality assurance activity — 21 CFR Sec. 211.186. This segment explicitly talks about the master production and control records for finished pharmaceuticals. Complying with the rules laid down in this section is vital for pharmaceutical companies to deliver product consistently between production runs and for batch-to-batch uniformity.
Production process also requires compliance with several of the key provisions of Current Good Manufacturing Practice (cGMP) regulations 211. Pharmaceutical companies can focus on implementing the keywords provided to set up a strong system complying with this regulation by understanding it well. Due to an increase in consumer trust, it will lead to quality improvement and ensure that regulatory bodies have a good relationship with businesses while promoting public health.
1. Development of Master Production and Control Records
Sec. 211.186(a) highlights the importance of uniformity from batch to batch in drug production. To do this, pharmaceutical firms should develop master production and control records for each drug product, covering all batch sizes. These records serve an important purpose by showing how a product is made and in maintaining the uniformity of quality.
Written process provides a general understanding about how to prepare the master production records and control records which come with various steps that are necessary. The records must be signed and dated by one person and verified by another person. . This allows for another level of approval in the sign-off procedure, ensuring the records are accountable and correct.
2. Master Production and Control Records: prime and must.
Sec. 211.186(b), which identifies what must be included as essential components of the master production and control records andcompliance requirement for each component diligently
a) Name, Strength, and Dosage Form–Provide the name and strength of the drug product with a description of its dosage form; The drug substance is followed by such information to avoid any ambiguity relating the identity of the drug product as it moves through manufacturing, testing and distribution.
(b) Active Ingredient Information: Records should include the name and weight or measure of each active ingredient per dosage unit or volume/weight of the drug product. Furthermore, there shall be stated, or should additionally show, the total weight or measure of any dosage unit. This knowledge is essential for appropriate formulation of the drug product and to ensure batch-to-batch consistency in both potency and efficacy.
c) Component List — The records shall contain a complete list of components, by name or code with sufficient specificity to identify any special quality characteristics. This ensures that there is a component list that includes all ingredients required for the drug product to avoid any errors or omissions.
(d) Weight system and variations: Master production and control records must include the weight or measure of an ingredient added to food using the same weight system (s), i.e., metric, avoirdupois or apothecary, that was used when determining scientifically substantiated critical limits. All records must explain any variations in the number of components required for preparation of dosage form within reasonable limits. By standardizing the weight system all members of the production team are held to the same measuring stick and thus providing a lower probability for errors.
e) Calculated Excess of Component- Source to be raised for any calculated excess of component with the description to avoid overages and its related quality issues. This limits contamination of ingredients in amounts that may become toxic or noxious due to the presence of certain elements.
f) Theoretical weight or measure – there should be a statement of the theoretical weight or measure at relevant points during processing to ensure that declaration is accurate throughout production. Think of theoretical weight or measure as a control figure, i.e., you can compare actual measurements to this measurement to see where things diverged (and errors might have happened during production).
g) Theoretical Yield: Describe the theoretical yield, in addition to the maximum and minimum percentages of the theoretical yield feasible beyond which an investigation, pursuant to § 211.192, is needed; Theoretical Yield being such a critical factor helps manufacturing units to determine the anticipated return that their production process should yield.
h] Contraindications: give a full description of container-closure and packaging components (for drug product, not drug substance). Submit a Specimen or Copy of Each Label and all other labelling to include the signature date by responsible personnel who approve the labelling. Recording the containers, closures and packaging materials which are used in production adds a level of protection against product stability and protect the drug product purity and security to guarantee accurate labeling during its shelf life.
3. Control and Process Design Documentation
Sec. 211.186, Master production and control records shall include complete manufacturing and control instructions, sampling and testing procedures, specifications, special notations, and correctives actions to be taken. These logs are critical as they tell us how to consistently reproduce the product and manufacture it consistent with the established quality standards.
a) Manufacturing Directions: The master production records should include clear, step-by-step instructions for every stage of the manufacturing process. Such instructions should be legible, non-contradictory and as simple as possible so that all production staff can carry out the procedures correctly.
b) Control Records: The control records should spell out the quality control methods and assays which must be conducted at particular manufacturing stages. They will tell you when anything is going bad, so that you can put a stop to its release.
c) Sampling Procedures: The sampling procedures must be clearly established and carried out systematically to ensure that the samples taken for testing are indeed a reflection of the entire batch. Good sampling guarantees the testing results genuinely exemplify the general standard of a product.
d) Testing Procedures: All testing procedures shall be of a high standard and comply with applicable regulations and industry standards. All test methods used must be proven, and the test equipment monitored, calibrated and maintained in a manner that confirms accurate results are being obtained.
Specifications: Records should specify the identity, strength, quality, and purity of the drug product. These specifications are used to measure the quality of the product and whether a batch is within standard.
Special Notations and Precautions: Document any special notations, precautions or other information which is required for the performance of product realization. These should be things like environmental requirements, the type of equipment that is in place or the critical control points of the process.
4. Training and Documentation
Compliance with Sec.211.186 — Preparation of Master Production & Control Records, not only requires the preparation of master production and control records, but also a well-trained competent workforce. Having personnel involved in manufacturing, quality control, and documentation trained appropriately in cGMP principles and the specific requirements of Sec. 211.186 is crucial.
The company can always organize regular training session, workshops and seminars for employees to keep them abreast with industry best practices, regulatory changes and any updates on the procedures of the company. Keeping a complete training program current is one of the primary measures to make sure everybody knows what they are supposed to do and how important their part in being compliant.
Good documentation practices are key factor in cGMP compliant environments. We cannot prove that the compliance to regulations without proper record-keeping and document control. A record should be kept of all steps in the preparation of master production and control records, manufacturing, testing, and quality control. Note that this sort of documentation requires systematically organized data that can easily be pursued over time or during inspection.
If your organization is interested, contact BioBoston Consulting or visit our website to find out more details.
