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CONTENTS◊ Introduction◊ Manufacturing & packaging

outsourcing◊ Commercial discussions◊ Confidentiality agreements◊ Technical agreements◊ Regulatory aspects◊ Validation◊ Deviation & change control◊ Re-assessment of principal

manufacturer◊ Contract analysis

CONTENTS

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CONTRACT MANUFACTURING is defined as the manufacture (or partial manufacture) of a product to the order of one person or organization (the contract giver or customer) by another independent person or organization (the contract acceptor or principal manufacturer).

Reasons why which customer give contract to principal manufacture for manufacturing his products:

They may not have sufficient capacity to produce the required volume.

May not have capability in terms of facility, equipment &/or competence to produce particular type of product .

LOAN LICENSE

AUDITING

CONTRACT MANUFAC

TURING

OUTSOURCING

INTRODUCTION

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GENERAL GUIDELINES ON MANUFACTURING & ANALYTICAL SERVICES OUTSOURCING{W.H.O. ,T.G.A.,M.H.R.A.}

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• Contract production & analysis must be correctly defined, agreed & controlled in order to avoid misunderstanding.(scope & role )

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• There must be a written contract b/w both (with clear established duties of each party).

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• Each batch of product for sale or issuing the certificate of analysis is released by authorized person with his full responsibilities is clearly stated in contract.

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• Customer should bear the ultimate responsibility for ensuring that the product specification complies with relevant legal requirements.

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• All arrangements for contract manufacturing & analysis should be in accordance with the marketing authorization for product concerned.

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• Contract should permit the customer to audit the facilities of principal manufacturing.

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• In case of the contract analysis the final approval for release must be given by authorized person.

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In this activities following three items must be clearly understood by both parties.

CONTRACT: It is an order placed by one party upon another may be constitute a legally

binding contract.

The contract could be constructed as having a legal meaning in term of legally binding document.

The contract shd be drawn b/w customer & principal manufacturer that specify all responsibilities related to manufacture & ctrl of product.

The use of phrase TECHNICAL AGREEMENT may be more acceptable to each party.

MANUFACTURING & PACKAGING OUTSOURCING

CONTRACT

CONTRACT GIVER

CONTRACT ACCEPTOR

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The product specification used by the principal manufacture comply with relevant legal requirement such as the marketing authorization & label declarations.

The product , as manufactured, meet the specification. The required quality is maintained during transport, distribution

& storage. All aspects of contract arrangements are carried out in

accordance with GMP. All work is carried out in premises covered by appropriate

licenses granted by local authorities

There is continued compliance to the agreement. Compliance to regulatory & statutory requirements relating to

warehouse & distribution practices is maintained.

CUSTOMER

PRINCIPAL MANUFACTURER

GENERAL RESPONSIBILITIES

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Point that are included in commercial agreement of Commercial / organizational matters are:

Exact definition of products & activities that are to be given to the principal manufacturer.

Financial responsibilities for supply of starting of packaging material.

Financial responsibilities for cost of rejection, losses, rework & failure.

Financial responsibilities for destruction of waste & rejects with consideration of any environmental aspects.

Terms & condition for payment.

The basis of price revision.

Financial standing of principal manufacturer & customer.

COMMERCIAL DISSCUSSION

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Assurance that the principal manufacturer continuously complies with good business practices.

Insurance provision.

Product liability responsibilities.

Stock levels to be held by principal manufacturer.

Planning , forecasting & lead time arrangements.

The period for which any agreement will run & the agreements for their termination.

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For the commercial well being of both parties, it is advisable to enter into legally binding agreements on matters of secrecy or confidentiality. such agreements serve to provide assurances, under law, that commercially sensitive information, which is property of principal manufacturer & not in public domain, is protected.

They should contain detailed information on technical responsibilities & quality matters relevant only to actual manufacture &/or assembly.

The principal manufacturer may also need to protect certain aspects of their customer operation.

In particularity , confidentiality of other customer’s work on the principal manufacturer’s site may come into question.

CONFIDENTIALITY AGREEMENTS

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Having established the acceptability of the principal manufacturer, the customer & him established the exact responsibilities of each party & state these in a formal agreement signed by representatives of all parties concerned.

GENERAL CONSIDERATION:

The responsibilities of the “Qualified persons” in the customer`s & the principal manufacturer`s organization.

Assurance that the principal manufacturer continuously complies with `good pharmaceutical practices` & relevant legislation.

Provision of reasonable access by the customer to the principal manufacturer`s premises.

Responsibility for changes or amendments to the technical aspects of the agreement.

Arrangements for changes or amendments to the technical aspects of the agreement.

Channels of communication.

Statements of assurance that the principal manufacturer will not undertaken processes or activities that could jeopardize the quality of the product.

TECHNICAL AGREEMENTS

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Finally agreement should be approved & technical responsibilities accepted by each party concern with agreement, preferably signed by the person responsible for quality in both organization.

Purchase &supply of starting materials.

Sampling , testing & release of starting materials.

Artwork for the text copy.

Purchase &supply of packaging materials.

Sampling , testing & release for use of packaging materials.

Bulk manufacture.

Sampling , testing & release of bulk product.

Assembly of finished pack.

TECHNICAL AGREEMENT RELATED ISSUES

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Sampling & testing of finished product.

Control and supply information.

Control and supply samples

Finished product release.

Transport and distribution.

Safety information.

Sub-contracting.

Miscellaneous responsibilities.

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Authorization of manufacture.

Product authorization.

Release for sale.

Customer release for sale.

Release for sale.

The requirements for the validation of processes are clearly established in current good manufacturing practices & other monographs . It is the responsibility of the customer to ensure that the principal manufacturer has validation any process to satisfy both the guidelines & the customer`s own internal requirements. These requirements also apply to the validation of cleaning processes both prior to & after production.

REGULATORY ASPECTS

VALIDATION

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DEVIATIONS :-

Deviation from anything that has been registered or agreed must be approved by customer before they are undertaken by the principal manufacturer.

Materials with a different specification to those stated in marketing authorization may have to be used where a supplier cease to supply a particular grade of excepients and no alternative is available.

The principal manufacturer may have to use other equipment if for example, existing equipment breaks down or where new equipments is purchased to improve the process throughput or quality.

The process may need to be modified to improve the quality of the finished product by the use of shorter heating time or the use of different mesh sizes for sieving.

DEVIATION & CHANGE CONTROL

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CHANGE CONTROL:-

Change control needs to be formalized b/w the principal manufacturer & the customer so that if there are any change in any specification document and process, the principal manufacturer is made aware of change are then made to his documents.

These then go back to the customer for approval so that he has the assurances that the principal manufacturer has made the change.

It is useful to record the timing of change and the first batch number of product to be made after the change.

Once full scale production has concerned the customer will secure a degree of confidence in the principal manufacturer's operation with specific individual.

These re-assessments should be carried out in same manner as the initial order & should include checks on areas of weakness identified at the first assessment & on improvement that were requested at that time.

RE-ASSESMENT OF PRINCIPAL MANUFECTURER

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The principal outline in this monograph apply to the analytical work contracted to the third party. In particular the following need to be addressed.

The requirement of GLP.

The specification & methods authorized in marketing authorization.

Validation of contract laboratory equipment & methods.

The method of reporting & certifying the result.

The reporting of spurious results & their relationship to the sample being analyzed, the other results obtained & the bulk which has been sampled.

Statistical evaluation if appropriate to the data.

CONTRACT ANALYSIS

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