If you are a pharmaceutical company in India with a turnover of more than Rs. 250 crores, you only have till July this year (2024) to adhere to the revamped Schedule M of the Drugs and Cosmetics Act, 1940, which aims to enhance the pharmaceutical quality control in India. Considering the volume of change – both from a qualitative and quantitative perspective, this will require significant changes in business processes and requires urgent attention. Even for small and medium pharmaceutical manufacturers, the time to adhere to Schedule M is less than a year away.
The revised Schedule M has brought about some new concepts in line with international manufacturing standards such as Pharmaceutical Quality System (“PQS”), Quality Risk Management (“QRM”), Product Quality Review, Complaints and Change Control. In addition to this, the Schedule has amplified the concepts that existed in the earlier Schedule such as use of computerized systems for risk assessments, equipment qualification, inspection and quality audit plans including suppliers’ audits and approval. The Schedule now has a total of 11 product specific requirements which extend to premises, equipment, personnel, quality control and risk assessment.
The Schedule has been broadly divided into two parts – Part I, laying out the main principles for manufacture of all pharmaceutical products and Part II to Part XIII which are product specific/technical standards on manufacturing processes, where specific requirements for the following have been freshly introduced –
- Manufacture of Hazardous substances such as Sex Hormones, Steroids or Cytotoxic substances (Part III)
- Manufacture of Biological Products (Part IV)
- Manufacture of Radiopharmaceutical Products (Part V)
- Manufacture of Phytopharmaceutical Products (Part VI)
- Manufacture of Investigational Pharmaceutical Products for Clinical Trials in Human (Part VII)
We have done a comparative analysis of Part I, which applies to manufacturers of all pharmaceuticals, between the erstwhile and revised Schedule M.
| Core Component | Earlier Schedule M | Revised Schedule M |
| Pharmaceutical Quality System (PQS) | The concept did not exist. | Senior management involvement mandatory in annual quality review throughout the life cycle of the product. Suppliers and distributors also brought within purview.
Definition and documentation of product quality system including management responsibilities. |
| Quality Risk Management (QRM) | The concept did not exist. | Assessment, control and review of risks to the product quality |
| Product Quality Review | The concept did not exist. | Regular product quality reviews with minimum defined criteria, especially those for export.
Timely corrective and preventive actions with documentation based on groups of product types |
| Sanitation and hygiene | Existing. More detailed | No substantial change |
| Good manufacturing practices for pharmaceutical products | Generic overview captured | Defined processes with systematic reviews for possible risks.
Records of all instructions and procedures to showcase history of products |
| Qualification and Validation | Existing, but with limited detail | Documentary evidence showcasing qualification and validation with regard to premises and processes specifically –
a. design qualification (DQ) b. installation qualification (IQ) c. operational qualification (OQ) d. performance qualification (PQ) |
| Complaints & Adverse Reactions | Existing, but with limited detail | Careful documentation and review of complaints and defective products with a designated person identified.
Written procedure mentioning action to be taken including recall. Informing authorities of faulty product. Establishing a pharmacovigilance system to collect, process and forwarding reports to licensing authorities for information on the adverse drug reactions |
| Product Recall | Existing, but with limited detail | Identification of personnel for execution and coordination of recalls.
Monitoring and recording of progress of the recall process |
| Change Control | The concept did not exist. | Establishing a formal change control system impacting the production
and control of the product. Revision of all documentation impacted by the change. |
| Production under loan license or contract and contract analysis and other activities | The concept did not exist. | Audit of facilities by the loan licensee on facilities and activities at the manufacturing premises |
| Self-inspection, quality audits and suppliers’ audits and approval | Existing, but with limited detail | Minimum and uniform standard of inspection at least once a year. Appointment of a self-inspection team consisting of experts in their
respective fields who are familiar with GMP. Supplier’s audit to be done before being approved. Effective follow-up programme by company management
|
| Personnel | Existing, but with limited detail | Adequate number of personnel having full knowledge of GMP.
Appointment of Key Personnel including heads of production, the heads of quality units and the authorised person. Detailed responsibilities, hygiene and training of personnel |
| Premises | Existing, but with limited detail | Premises to conform to Factories Act and to be used only for the manufacture of pharma products |
| Equipment | Existing, but with limited detail | Cleaning of equipment on a fixed schedule.
Layout and design of equipment to be planned in a way to minimise contamination. Clear labelling and pipework Maintenance of current drawings of critical equipment and support systems |
| Documentation | Existing, but with limited detail | Copious documentation and records of materials, methods and control measures used for each batch processed.
Formally authorised master formula for each product and batch size to be manufactured with minimum specifications |
| Good practices in Production | Existing, but with limited detail | Alignment of manufacturing processes with license.
Access controls in production area Restriction on operations on different products simultaneously or consecutively Appropriate technical measures to prevent contamination Periodic checks/environmental monitoring on measures to prevent cross contamination |
| Good practices in quality control | Existing, but with limited detail | Sampling and QC function to be independent of production, recording and investigating deviations.
Minimum testing certifications from suppliers |
| Computerized Systems | Existing, but with limited detail | Validation of GMP related computerised systems
Operational qualification reviews of hardware and software Retrospective validation of an existing system Secure back up system to ensure there is no loss of data Additional check on manually entered critical data |
| Site Master File | Existing | Following added –
i. Quality management system of the company, PQS and QRA ii. Documentation system, change control, validation policy and product quality review |
Lexplosion Solutions Private Limited is assisting a number of pharmaceutical companies through their journey of setting up internal processes and implementing regulatory changes required as a fallout of the revamped Schedule M. Do reach out to us at koushik.sinha@lexplosion.in for further details.
Written by: Ananya Shukla
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