COMMENTS ON THE DRAFT GUIDELINE ON GOOD DISTRIBUTION PRACTICES FOR PHARMACEUTICAL PRODUCTS

 

                        - Ganadhish Kamat

On 4th of April 2024, CDSCO issued draft guideline on Good distribution practices for Pharmaceutical products. This draft is similar to the draft issued for comments in 2018 with few additions like Quality Risk Management , Quality system requirements, Management review etc. As usual the guideline has been copied from WHO guideline without trying to understand the distribution chain within India and evaluating suitability of WHO guideline for distribution within India.  Obviously there are many clauses, statements and terms which are not applicable in India and create confusion rather than providing clarity. I wish CDSCO had applied the principles of Quality Risk Management (which it is trying to introduce everywhere) while finalizing the draft.

Given below are some of my observations / comments on the guideline. Since CDSCO does not pay any attention to comments submitted by industry experts, this time I have decided not to submit my comments to CDSCO. I am however writing them in my blog for my own satisfaction and for those who may be interested in reading them and submitting them to CDSCO.  

Comments -

3.0 – Scope – States that “These guidelines are intended to be applicable to all persons and outlets involved in any aspect of the storage and distribution of pharmaceutical products from the premises of the manufacturer of the product to the person dispensing or providing pharmaceutical products directly to a patient or his or her agent”.  Clarification is required whether all the causes are applicable to all entities in the distribution chain including transporters and retailers or these clauses apply selectively to certain entities because the guideline is not clear about the same and many clauses are not feasible to be implemented at all the levels.

4.5 – Requires agreement to be in place with all the individual agencies involved in the storage, transportation and distribution. It is however not clear who has to sign the agreement and with whom. Should the manufacturer sign agreements with all agencies including CFAs, wholesalers, transporters, retailers or each entity has to sign with the agencies they are dealing with?

5.1 – Requires entities involved in the storage and distribution of pharmaceutical products to have a comprehensively designed, documented and correctly implemented quality system that incorporates GSP, GDP, principles of quality risk management and management review. It is not clear whether this apply to only manufacturers or to all the entities such as CFAs, wholesalers, distributors, transporters & retailers etc.

10.10 – Requires procedures to be in place to ensure safe, transparent and secure distribution system which includes product traceability throughout the supply chain. Clarification is required as to what controls are expected to ensure that the product is not replaced with spurious in transit? Is it expected that the vehicle be sealed with unique seal to be opened only by the recipient? Only foolproof method will be establishing track and trace system in the entire distribution system through 2D Barcodes or QR codes.

10.13. – Requires measures to be in place to ensure that pharmaceutical products have documentation that can be used to permit traceability of the products throughout distribution channels from the manufacturer/importer to the entity responsible for selling or supplying the product to the patient or his or her agent. In India sometimes there are multiple distributors of one company in the same city or district.  A retailer may source a product from multiple distributors based on stock availability, how can they establish which patient received product from which distributor? Sometimes retailers even get the drug from nearby retailer to avoid sending the patient back. How such cases are to be handled? Full traceability will be possible only with elaborate documentation & segregation of each supply and sale. Alternatively as mentioned earlier track and trace system will have to be introduced throughout the country.

11.5 – Requires segregated & designated storage areas for the pharmaceutical products in quarantine, released, rejected, returned or recalled products as well as those suspected to be spurious. Revised Schedule M allows use of electronic controls in lieu of designated areas. This requirement contradicts the requirement in Schedule M, especially because both are applicable for warehouse in the manufacturing unit. As the storage area required for Quarantine, release, rejected products often vary dynamically, having fixed designated areas could result in wastage of space or non-compliances. Such controls do not provide added security when electronic controls are in place.

11.12. – Requires FEFO (first expiry/ first out) system to be followed for selling and/or distribution of products. Exceptions shall be permitted as appropriate, provided that adequate controls are in place to prevent the distribution of expired products. Distributors often hold back short shelf-life stocks and distribute newer inventory to avoid returns. Also, distributor may want to distribute older stocks in the areas where the uptake is fast & newer stock to places where the uptake is slow to avoid returns. While it is important to prevent distribution of expired stocks, enforcing FEFO system will result into multiple exceptions. To adopt such system at retailer level, every retailer will have to go for automation.  

11.14 – The requirement is similar to 11.5

12.1 – Requires storage and handling conditions to comply with applicable National regulations. It is not clear as to which National regulations are to be followed.

12.4 – Requires records of storage conditions to be kept for at least the shelf-life of the stored product plus one year. As the inventory in the storage places keep changing and storage conditions records are not product or batch specific, such document retention policy based on shelf-life is not suitable for storage condition records.

12.7 – Requires maintaining records of stock and updating them after each transaction (e.g. entries, issues, losses, adjustments). Periodic stock reconciliation is required to be performed at defined intervals, by comparing the actual and recorded stock. 12.8 & 12.9- requires documented investigation of any stock discrepancies, identification of root causes and CAPA. Are retailers also required to comply with all these requirements including the periodic stock reconciliation?

13.4 – Requires written agreement between the manufacturer, Government Institution, agent and Transport Company. Clarification is required as to which government institution should be part of the agreement. Secondly the transporter mentioned here is the one which carries goods from the manufacturing plant to distribution warehouses and CFAs or also include those involved in subsequent stage transportation such from distributor to retailers.

13.6 – 13.9 – Specifies requirements pertaining to maintaining storage conditions as per label during transportation, identifying and investigating any temperature deviations, reporting to distributor etc. This is important for ensuring quality of drugs. Manufacturers, CFAs & distributors need to understand the implications of this requirement and make appropriate arrangements and build into their costing. Each shipment will have to include data logger. Since stability in India is done at 30°C, and since the temperature in most parts often go above 32°C, practically all shipments of APIs and drug products irrespective of  labeled storage condition needs to be transported in temperature controlled vehicles.  Clarification is required whether these controls are required for all the transportations (including those within city) or only for long distance transportation with transit time beyond certain limit.

13.15 – Requires drivers of vehicles to identify themselves and present appropriate documentation to demonstrate that they are authorized to transport the load. What kind of documentation will be considered as appropriate?

13.19 – Requires procedures to be in place for the operation and maintenance of all vehicles and equipment involved in the distribution process, including cleaning and safety precautions. Is the agency expecting SOP for driving, maintenance and cleaning of all the vehicles involved in transportation of the drugs?

13.24 – Requires temperature monitoring records during transportation to be kept for a minimum of the shelf-life of the product distributed plus one year. As explained earlier since these records may not be product or batch specific, such requirement in terms of the shelf life of the product is not suitable.

13.31 – Requires adequate measures to be taken to prevent unauthorized entry and tampering of the vehicles, so as to prevent the theft or misappropriation. Does this mean that all goods are to be transported (even short distances) in sealed vehicles?

15.2 – Requires the contract acceptor for transportation of the pharmaceutical products, is aware of the pharmaceutical products to be distributed and complies with the appropriate storage and transport conditions prior to the dispatch of pharmaceutical products. Does this mean all transportation (even short distances) need to done using transporters who have signed contract agreements?

15.3 – Requires dispatch and transportation of pharmaceutical products to be undertaken only after the receipt of a valid delivery order or material replenishment plan. Does this apply to even shipments from distributor to retailers?

15.7 – Requires distributor to ensure that the volume of pharmaceutical products ordered does not exceed the capacity of storage facilities at the destination. How will distributor know the available storage capacity at the end of the receiver?

15.8 – Prevents supply or receipt of pharmaceutical products after their expiry date, or close to the expiry date. Such movements are required to be carried out for product returns for destruction.

15.9 – Requires incoming shipments to be examined to verify the integrity of the container/closure system, to ensure that tamper-evident packaging features are intact, and that labelling appears intact. Such examination at Central warehouses, CFAs and distributors, will require opening of shipper boxes and hence not practical nor advisable.

16.15 – Requires mechanisms to allow for transfer of information, including quality or regulatory information, between a manufacturer and a customer, as well as the transfer of information to the relevant regulatory authority as required. Clarification is required as to who is considered as customer in this statement and what kind of information is referred to.

17.0 COMPLAINTS & 18.0 RECALLS AND RETURNS – Requirements related to these are adequately covered in Schedule M. Again specifying them in this guideline does not serve any purpose and can only create confusions about who in the distribution chain need to carry out activities such as investigation and record keeping.

22.0 – SELF-INSPECTION – Clarification is required as to which levels in distribution chain this requirement is applicable.