H. PRODUCTION AND PROCESS CONTROLS

I. MASTER AND BATCH PRODUCTION RECORDS

Provide a blank Master Production Record (MPR) to show the operating procedures for each step in the production process. The MPR should be signed by responsible department heads to demonstrate how the document became the official version.

Describe your procedure for the preparation and endorsement of Master Production Records (MPR). Give reference to the written protocol.

This procedure must describe the following:

a. The individual (title) responsible for the development of the MPR;

b. All individuals responsible for signing (endorsing) their approval of the MPR;

c. How and where the MPRs are stored; and

d. The Change Control Procedure for updating MPRs and eliminating obsolete ones; and

e. Releasing the currently official version of the MPR to production personnel for use as a Batch Production Record.

1. Master Production Record, Exhibit

At this point in the DMF, you can provide a copy of a blank Master Production Record.

2. Batch Production Instructions

The Batch Production Record (BPR) should be an accurate reproduction (copy) of the MPR, the only difference being a batch number having been assigned to it.

Describe the batch numbering system. Explain the significance of each series of numbers, characters or symbols in the numbering system.

Describe who is responsible for releasing blank BPRs to the production personnel.

Describe who is responsible for the review and approval of executed (completed) BPRs

II. IN-PROCESS SAMPLING PROCEDURE

Based on the MPR, describe the in-process sampling procedure employed during production, i.e., number of samples, quantity of each sample, at what station, etc.

1. Raw Material

Describe the procedures established by Quality Control for the sampling of raw materials. This description should include, but should not be limited to, the following:

a. A reference to the SOP governing the sampling of raw materials;

b. Location and description of the sampling area;

c. Procedure to assure quick resealing of sampled raw material containers;

d. Approved/Rejected material protocol;

e. Describe your procedure for maintaining valid analytical standards for the raw material tested; and

f. Include an original specimen of each label and form associated with Raw Material Sampling.

2. Containers and Closures

Describe the procedures established by Quality Control for the sampling of containers and closures. This description should include, but should not be limited to, the following:

a. A reference to the SOP governing the sampling of containers and closures;

b. Number sampled (Square root of N + 1, etc.);

c. Location and description of the containers and closures holding area;

d. Identification of containers and closures which have been sampled and/or pending approval/rejection;

e. Approved/Rejected material protocol;

f. Describe your procedure for maintaining a valid product standard; and

g. Include an original specimen of each label and form associated with approving/rejecting sampled containers and closures.

3. In-Process Material

Describe the procedures for in-process sampling. Describe who is responsible for carrying out the sampling. Include any SOPs that describe how samples are to be taken, e.g., use of a sector probe for dry powders.

Include an original specimen of each label and form associated with In-process Material Sampling.

III. FINAL PRODUCT SAMPLING PROCEDURE

Describe the procedures used in production regarding final product sampling, sample analysis and approval or rejection. Give an example as to how you take random samples from a batch.

Describe the procedures established by quality control for the sampling of Final Products. This description should include, but should not be limited to, the following:

a. A reference to the SOP governing final product sampling;

b. Number of containers sampled (Square root of N + 1, etc.);

c. Location and description of the sampling area;

d. Identification of material which has been sampled and/or pending approval;

e. Procedure to assure quick sealing of sampled containers;

f. Approved/Rejected material protocol;

g. Describe your procedure for maintaining a valid product standard; and

h. Include an original specimen of each label and form associated with Final Product Sampling.

IV. REPROCESSING PROCEDURES

Written procedures shall be established and followed prescribing a system for reprocessing batches that do not conform to standards or specifications and the steps to be taken to insure that the reprocessed batches will conform with all established standards, specifications and characteristics. Reprocessing shall not be performed without the review and approval of the quality control unit. 21 CFR 211.115.

A reprocessing procedure should be unique for each individual product. Specific reprocessing steps should be described in a Type II DMF. The Type I DMF may contain a general description of your reprocessing policy.

Include an original specimen of all identification labels associated with the control of reprocessed goods.

V. PACKAGING AND LABELING

The Quality Control department must have written procedures for the control of packaging and labeling components. These procedures shall describe the acceptance and rejection criteria as well as reconcile the quantities of each component (drums, liners, seals, and inner/outer labels) requested, issued, used, and returned.

The Quality Control department must have written procedures for label issuing, reconciliation and record keeping. The procedure shall reconcile the quantities of labels issued, used, returned, and destroyed.

Instructions for packaging and labeling must be included in the MPRs. All packaging and labeling components must be identified in the records.

Give reference to, and/or a copy of, your SOP governing this.

Include specimens of all other identification labels not previously included in any other section of this DMF.