Of all the campaigns the Central Drugs Standard Control Organisation (CDSCO) has carried out in India, its sustained training programmes intended at educating the drug industry, especially the small scale sector, on the need to switch over to a Good Manufacturing Practice as prescribed by the revised Schedule M of the Drugs and Cosmetics Rules 1945, has been one of the most important.
The months long effort, with Ashwini Kumar, the DCGI playing a key role, has been a success if the interest shown by the industry to adapt to the new changes in tune with the regulatory requirement is any indication.
The CDSCO has covered all parts of the country (except the West where the CDSCO West Zone Office is doing commendable job in this direction) through four representative workshops in which the cream of the SSI drug sector participated with much enthusiasm. The speakers were from the CDSCO of different zones, industry subject experts and also from the SSI itself. The fifth and the last in the series of CDSCO programmes will take place at Jaipur soon.
The workshops, which took place in Delhi, Kolkata, Lucknow and Chennai were organized by CDSCO while it played a major role in disseminating information in a number of other workshops organized by the drug industry associations at different states. The common theme was "revised Schedule M " and Indian drug industry is today well aware what it means to them.
The industry is aware of the significant changes they have to undergo in five areas - the documentation, the validation of procedures and calibration of instruments, increase in area, air handling systems and the stability studies. Other areas of importance include preparation and use of Standard Operating Procedures (SOP), Training, Water Systems, cross-contamination and mix-ups etc.
The new GMP is a progressive step initiated by the central government with an intention to help the industry grow global. Even though the CDSCO could have remained silent after notifying the changes, and wait to see the implementation of the changes by the industry and the monitoring of its compliance by the state drug control authorities, it has taken a pro-active role and had been trying to create as much awareness as possible during the last several months.
The topics routinely covered by the department included the implementation of revised Schedule M by SSIs, site master file and its importance, stability studies of pharmaceutical formulations, SOP - how to write and maintain in the work place, master validation plan and its proper implementation, design, layout and utility requirements for small scale pharmaceutical (formulation) unit, cleaning, sanitation and prevention of cross contamination required to be maintained during manufacture of pharmaceutical formulations, air handling units and its utilization in the pharmaceutical formulation units, clean room concept and its implementation to manufacture sterile pharmaceutical preparations.
During the workshops the views of the Small Scale Manufacturers were also noted as they were asked to view their misgivings by way of talks and panel discussions. It has been emphasized to the SSIs to organize small workshops locally on subject specific issues. The department is confident that all serious players in Indian pharmaceutical industry would switch over to revised GMP, thereby heralding a new era in its history. The role of drug inspectors for inspection of manufacturing premises should eventually be that of a GMP auditor and facilitator. CDSCO is doing its best to bring in the changes.
Validation
Among these essentialities of the revised GMP, validation is perhaps the easiest one to be implemented by the drug industry. There is practically very little expense involved, as it's solely about proper documentation and doesn't call for any capital expenditure or introduction of additional facility. Despite the fact, validation remains to be the least understood clause among all other requirements.
Lets now try to understand more about validation, which is often considered as a difficult task by many an industrialist.
Validation is just a documented proof that everything, within reasonable certainty, that is involved in the manufacture of a product is under control. This includes the facilities, environment, materials, equipment and the processes including manufacture and cleaning procedures. It is meant to establish the quality of the final product through documented evidence. The assurance comes from the proven logic that a planned process will consistently perform giving the intended specified outcomes.
Validation studies, which include validation of processing, testing and cleaning procedures are essential part of GMPs and are conducted as per the pre-defined protocols.
The core of validation comes as a summarized written report on the recorded results and conclusions.
On the basis of validation studies processes and procedures are established and periodic revalidation undertaken to ensure that they remain capable of achieving the intended results. Critical processes shall be validated, prospectively or retrospectively.
The revised schedule insists that for any new master formula or method of preparation there is a need to demonstrate its suitability for routine processing and for achieveing the intended pharmacological action. This simply means that the defined process, using the materials and equipment specified shall be demonstrated to yield a product consistently of the required quality. Similarly, any significant change to the manufacturing process, including any change in equipment or material that may affect product quality and / or the reproducibility of the process, will have to be validated.
Master validation plan is a document pertaining to the "whole facility" that describes which Equipment, Systems, Methods and Processes will be validated and when they will be validated. It also includes Re-Validation- why and when.
There are two types of validation, the prospective and the retrospective.Validation conducted before manufacturing a new product or manufacturing a product after making planned changes in the process which can have a gearing on the products quality is prospective and the validation of a process already in production based upon accumulated production, testing & control data, i.e., past records in the possession of the manufacturer becomes retrospective.
Validation consists of: Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ).
DQ is necessary when planning and choosing equipment or systems to ensure that components selected will have adequate capacity to function for the intended purpose.
IQ is the qualification of a piece of equipment. The details of the equipment should be critically tallied with the order placed with the vendor. All critical components of the equipment should be tabulated and only after successful verification should the equipment qualified as conforming to IQ.
OQ outlines the information required to provide evidence that all the components of a system or equipment operate as specified and involves testing of normal operation controls, all alarm points, all switches, all displays, interacting controls or any other indications of operation & functions. Sometimes the manufacturers of some equipment carry out IQ and OQ of their equipment if these are included in the purchase contract.
PQ is to be carried out after both IQ and OQ have been successfully completed. It describes the procedures for demonstrating that a system or piece of equipment can consistently perform and meet required specifications under routine operation, and where appropriate, under worst-case situations.
- The author is with CDSCO (North Zone)