08.04.2014 |

LOGFILE No. 15/2013 - Drugmakers and Contractors

Relation between Drugmaker and Contractor

Extract from “Managing Contract Manufacturers and Testing Labs

It is in the nature of things that when a drugmaker assigns a contract, a portion of the information about the manufacture of the preparation in question moves beyond its immediate reach. Therefore, drugmaker and contractor alike must enjoy a considerable level of trust. To help build this trust, one effective approach involves establishing at an early stage close and permanent contact with the contract manufacturer. To build trust, both parties should share know-how and a general culture of communication, along with a readiness to provide information, an understanding of audits and absolute transparency regarding errors. Practice and day-to-day business eventually should reveal how the collaboration actually works.

Many drugmakers hold marketing authorizations for several preparations with differing dosage forms. This often means selecting a number of different contract manufacturers with different core businesses (e.g., specialization in particular APIs, dosage forms and manufacturing technologies).

Factors such as delivery date and quotation price still play a large part in the selection of a contract manufacturer. Drugmakers should also consider how the two parties work together during day-to-day business, particularly if problems arise during manufacture. How does the contractor handle problems? How quickly does it provide information? What solutions does it suggest? Drugmakers should get to know the relevant responsible person at an early stage to gain a first impression about the contract company’s level of understanding of basic pharmaceutical matters and a rough view of the production processes.

Responsibilities of the client

Drugmakers often share the opinion that collaborating with one contract manufacturer suffices. In contrast, other drugmakers favor assigning a particular preparation to several contract manufacturers. In that manner, should any problems with delivery reliability or quality arise, the drugmaker can switch production quickly to an alternative contractor. In principle, of course, a client likely would find it easier to communicate with a smaller stable of contractors. Drugmakers also should bear in mind the considerable investment required in qualifying additional or alternative contractors. They must both select and audit the best candidate. Even then, if the drugmaker commissions the alternative contractor to carry out production, in addition to defining all responsibilities in a contract, the contractor also must manufacture three validation batches.

A well-functioning business relationship generally does not require the appointment of an alternative contractor. Experience shows that a good partner contractor generally communicates only what is absolutely necessary. That means the drugmaker places an order for a defined quantity and by a defined deadline, and that the contractors delivers the goods in qualitatively faultless condition on the agreed delivery date and at the agreed price.

Definition of the requirements of the task

The drugmaker’s individual in-house departments set different priorities. So, a commercial- and planning-oriented department, responsible for purchasing and the assignment of contracts and compliance with delivery dates, would make its assessments based primarily on price and delivery reliability. In contrast, a department dealing with the assessment of contractors, specifically with audits and approval, would make an assessment based on GMP principles and according to an appreciation of quality-management issues. Thus, the drugmaker must define the requirements of the task. The contractor agreement has shown itself to be a beneficial tool fo r this type of definition. Therefore, the drugmaker and contractor together should agree, in the form of a contract, to all requirements and arrangements before the start of production.

Handover of the necessary documents to the contractor

The drugmaker must hand over to the contractor all documents relevant to the transfer of a drug product. On the one hand, the drugmaker in doing so hands over a large part of its know-how about a preparation. On the other hand, the contractor absolutely must receive this information, along with results from the documents, in order to assess its in-house manufacture, packaging and analysis. The documents include primarily the following:

  • Sections of the application file for marketing authorization 
    The contractor needs in particular the sections defining the details of the manufacturing, packaging and analytical procedure, with accompanying instructions and specifications. The drugmaker often sees these as the only documents that enable the contractor to compile manufacturing instructions.
  • Manufacturing instructions and batch production records 
    If the drugmaker has already manufactured a preparation in-house, it should hand over the relevant manufacturing instructions to the contractor. These manufacturing instructions contain both a detailed description of the manufacturing procedure and the setting parameters for the facilities and machines used. It is certainly helpful if the drugmaker hands over the batch production records or at least allows them to be accessed. All deviations from specifications and manufacturing-area staff notes should be apparent.
  • Test procedures and test protocols 
    As with the manufacturing instructions and records, the documents available to the drugmaker that address analysis remain in need, all in order to appropriately transfer the analysis of a preparation to a contractor.
  • Validation documents 
    If the drugmaker already has validation documents in-house, it is essential that it hand them over to the contractor. From these, the contractor can see, for example, an assessment of the limits and setting specifications as determined previously for the facilities and machines. In addition, the drugmaker will have already determined and defined the critical processing steps. Using the previously determined results, the contractor therefore can compile the risk analysis and the validation protocol much more quickly.

Approval of manufacturing instructions

A working change management system starts with the drugmaker’s approval of the manufacturing instructions. This ensures that the drugmaker receives notification of all changes and deviations at an early stage. In addition, it guarantees that the contractor always carries out production in accordance with valid manufacturing instructions approved by the drugmaker. The contractor must communicate all changes to the client; the changes then must be documented in a new version of the manufacturing instructions.


Extract from “Managing Contract Manufacturers and Testing Labs