SOP On In-process Control During Tablets Manufacturing
In-Process Control during tablet Manufacturing (IPC) refers to the careful monitoring and verification of critical parameters and quality attributes at various stages of tablet manufacturing. From the moment raw materials enter the facility to the point where the final tablets are ready for distribution, IPC ensures that every step of the process adheres to predefined standards and specifications. By proactively identifying deviations and addressing them promptly, IPC safeguards the integrity and consistency of the tablets, resulting in safe and effective medications for patients.
In-Process Control is a series of checks and balances that are integral to producing high-quality tablets:
1. Raw Material Control: The process begins with rigorous testing and evaluation of incoming raw materials. This step ensures that the materials meet the required quality standards before they are incorporated into the formulation.
2. Blend Uniformity Testing: Blending is a critical phase where various components of the tablet formulation are mixed together. Blend uniformity testing ensures that these materials are thoroughly combined, preventing the formation of hotspots or clumps that could impact the final tablet’s quality.
3. Granule Characterization: Granulation is the process of transforming raw materials into granules that can be compressed into tablets. IPC ensures that these granules possess the necessary properties for optimal flow, compressibility, and uniformity.
4. Compression Force and Tablet Weight: The tablet press operation is closely monitored to maintain the desired compression force and tablet weight. This control measure ensures that tablets have consistent hardness, size, and weight, which are crucial for proper dosing and patient adherence.
5. Friability and Hardness Testing: Tablets must be durable enough to withstand handling and transportation. Friability and hardness testing assess the tablet’s resistance to abrasion and its ability to maintain its structural integrity.
6. Dissolution Testing: Tablets are designed to release the active pharmaceutical ingredient (API) over a specific timeframe. Dissolution testing evaluates how quickly the tablet dissolves in simulated physiological conditions, ensuring the API’s effective release for optimal therapeutic outcomes.
To lay down the procedure for In process Controls during Tablet Manufacturing.
Implementing an effective process Controls strategy during tablets manufacturing is indispensable for several reasons:
1. Ensuring Quality and Consistency: IPC prevents deviations from quality standards, resulting in consistent tablet characteristics and efficacy.
2. Early Detection of Deviations: IPC allows for the early identification of issues, enabling prompt corrective actions to be taken before they escalate.
3. Regulatory Compliance: Compliance with strict regulatory standards is ensured, minimizing the risk of recalls or regulatory sanctions.
4. Process Optimization: Continuous monitoring of critical parameters enables manufacturers to optimize processes for efficiency and quality.
This SOP shall be applicable for in process controls during tablets manufacturing of pharmaceutical company.
Production /Quality Assurance Executive/Officer shall Be responsible for follow the procedure mentioned in this SOP.
Head Quality Assurance shall be accountable for compliance of SOP.
Abbreviations and Definitions:
- SOP: Standard Operating Procedure
- IPQA: In-process Quality assurance
- DT: Disintegration Test
- Carry out line clearance at each stage of operation prior to start up of the activity as per SOP.
- Check & ensure that machine equipment /Accessories bears the machine / bin/ container status label of current batch as mentioned in SOP.
- Verify that all the entries are completed in Batch Manufacturing Record (BMR) upto the previous stage of that activity.
- Verify the Relative humidity (RH), temperature and pressure differential of granulation room, which should be within the specified limit and record the observation for RH and temperature attached with BMR.
- Check integrity of sieve visually before and after sifting.
- Withdraw the final blend sample after completion of blending as per SOP and submit the withdrawn sample to Quality Control (QC)Lab for analysis.
- Ensure that blend is analyzed and released by QC. Affix the ‘Approved Label’ before start up of the compression.
- Check that the bin to be used for compression bears the product status label and is fixed on the machine at gravity feed receptor in such a way that there is no spillage of powder.
- Ensure that the status label is affixed on the machine /container/ bin.
- Ensure that all parameters of compression are being checked at startup of compression and results are within specified limits.
- Ensure that compressed tablets are analyzed and released by QC. Affix the ‘Approved Label’ before the start up of coating.
- Ensure that correct coating material is being used for coating.
- The weight of the tablet after coating should be within specified limits.
- Check the RH, temperature and pressure differential of the granulation, compression, coating, inspection and primary packing room and ensure that these are within specified limit. Record the observation.
- Carry out following In process checks at a frequency specified in the Batch manufacturing Record.
- Gross weight of 20 tablets
- Disintegration Time
- Individual weight variation of 20 tablets.
- Dispensability (if applicable)
For checking Individual weight variation collect 20 compressed tablets from a continuous run through discharge chute from each side(For double rotary) and record the weights of individual tablets/attach the printouts of individual weights in Batch Manufacturing Record.
In case the weight of tablet is not found within specified limit, segregate the containers filled between previous and current checks. Randomly collect 20 tablets from each container and take the weight of individual tablet.
Clear the container if sample passes the limit of weight variation. Recheck if any of container found having weight variation out of limit.
If the tablets from container in question fail second time, treat those tablets as ‘Recoverable’, which were compressed between the last check (By Production or IPQA whichever was latest) and present check.
Reset the machine and recollect the sample as stated above and check.
If all the 20 tablets are found within specified limit then allow for further compression.
Collect 06 tablets from continuous run from each side and perform Disintegration Test as per SOP.
If residue of the any tablet remains on the screen having palpably firm (i.e. hard mass), then stop the production and get the compression force of the machine adjusted.
Recheck for DT with another six tablets and if it passes then allow continuing the compression. If tablets form containers in question fail second time, treat those tablets as ‘Recoverable’ which were compressed between the last check (By production or IPQA whichever was the latest) and present check.
Perform Friability test as per SOP.
Ensure that all the parameters are being checked by production at a regular interval are within specified limits and the same has been recorded in BMR.
Collect the samples of compressed tablets after completion of the compression and submit it to Quality Control for analysis.
Check the results of analysis for compliance before clearance for packing/coating.
Verify that Yield reconciliation is being done and found correct at the end of each operation of compression.
If any deviation is observed during in process checks, investigate the cause of deviation and ensure that deviation will not affect the quality of product. Get the approval of head QA for deviation. Mention the same in the Batch manufacturing Record.
Carry out following In process checks at a frequency specified in Batch Manufacturing Record.
Gross wt. of 20 tablets
Ensure that all the parameters being checked by production/IPQA at regular interval are within specified limits and the same has been recorded in BMR.
Collect the samples after complete coating lot wise (If applicable) and check the appearance and gross weight. If found beyond limits then, ask production for corrective action and make deviation if required.
Collect the samples of coated tablets after completion of the coating and submit it to Quality Control for analysis along with Test request form.
Verify that Yield reconciliation is being done and found correct at the end of each operation of blending, compression, coating inspection.
If any deviation is observed during in process checks, investigate the cause of deviation and ensure that deviation will not affect the quality of product. Get the approval of head QA for deviation.
FORMS AND RECORDS
In process Checks of tablets -Annexure – I
- Master Copy – Quality Assurance
- Controlled Copies – Quality Control, Quality Assurance, Production
Reason for Revision
In-Process Control during Tablets Manufacturing is a meticulous and proactive approach that safeguards the quality, safety, and efficacy of pharmaceutical tablets. By implementing robust IPC measures, manufacturers demonstrate their commitment to producing medications that meet the highest standards and regulations. Ultimately, IPC ensures that the tablets that find their way into patients’ hands are not only safe but also potent, reliable, and effective, contributing to better patient outcomes and improved public health.