CHAPTER 8

DOCUMENTATION

Ref.

32º WHO

MASTER FORMULA

YES

NO

1

Section

14.22.

18.24

Is there an updated master formula for each product and size of lot to be  manufactured?

Does the Technical Director and/or Quality Control/Assurance Director authorize all master formulas?

1.1

Section

14.22.

18.27

If it is necessary to modify the master formula, are there written procedures on how to do this?

1.2

Section

14.22.

Is the Regulatory Health Authority notified of this change?

1.3

Section

14.22.

Is authorization from the Health Authority expected before undertaking the change?

2

Section

14.22

Does the qualitative and quantitative formula agree with the authorization given by the Regulatory Health Authority?

2.1

If a qualitative and quantitative formula change is made, is the corresponding authorization requested?

3

Section

14.23

Do all products have a master formula containing:

3.1

Section

14.23(a)

Product name, code and product number?

3.2

Issue date?

3.3

Section

14.23(b)

Description of pharmaceutical dosage form, concentration and/or strength of the active ingredients?

Ref.

32º WHO

MASTER FORMULA

YES

NO

3.4

Product shelf life?

3.5

Section

14.23(b)

Batch size?

3.6

Unitary formula?

3.7

Industrial formula?

3.8

Section

14.23(c)

Starting materials, indicating the quantity of use for each one, with the code or number related to their specifications including those starting materials that are used up during processing and their equivalence to their International Nonproprietary Names (INN)?

3.9

Section

14.23(d)

Theoretical intermediate yield and theoretical final yields with their correspondent limits?

3.10

Section

14.23(e)

Indication of the areas in which each one of the process steps occur and equipment used?

3.11

Excess active ingredients (if occurs)?

3.12

Names and signatures of the qualified people involved in the issuance, review, and approval (at least two)?

3.13

Section

14.23(g)

Detailed instructions of the steps to follow for each stage of the process?

3.14

Section

14.23(h)

Instructions concerning controls during the process, of intermediate products and operational variations, indicating specifications?

3.15

Section

14.23 (f)

In the master formula, are there references to the SOPs related to different stages of manufacturing, equipment operation, etc. when they correspond?

Ref.

32º WHO

MASTER FORMULA

YES

NO

3.16

Section

14.23(j)

Special precautions that should be taken during the different stages of the process due to the characteristics of the starting materials handled and equipment.

3.17

Section

14.23(i)

The standards for the storage of the intermediate or bulks, including the container, the labeling and any other storage condition when the product

requires it?

3.18

Formula review date.

3.19

Number of Health registry.

3.20

Indication of processes (validated) for the manufacture of the product.

3.21

Forms for record keeping of product specifications during manufacture process (weight, hardness, friability, closure of capsules, disintegration, viscosity, etc.) performed by production and quality control

4

Section

14.26

Is a production order issued for each batch of processed product?

5

Section

14.26

Does the production order issued adjust to the master formula of the product?

Ref.

32º WHO

BATCH PROCESS RECORD

YES

NO

5.1

Section

14.26

Is there a process of credible transcription that ensures its exact reproduction?

5.2

Section

14.28

Do responsible personnel authorize it?

6

Section

14.28

Does it contain the following data:

6.1

Section

14.28(a)

Product name?

6.2

Section

14.28(c)

Issue date?

6.3

Sections

14.28(b) and

14.28(e)

Batch number?

6.4

Section

14.26f

Expiry date of finished product?

6.5

Section

14.28(b)

The list of raw materials involved (including the ones that are used up during processing) with their code numbers, lot, and/or analysis, theoretical and real quantities utilized for each of them?

6.6

If it is necessary to adjust the concentration of raw materials, is the modification signed by a qualified person?

6.7

Section

13.14.

Are the labels of the raw materials separated, attached?

6.8

Section

14.28(f).

Is the detailed description of each one of the steps included in the processed lot record?

Ref.

32º WHO

BATCH PROCESS RECORD

YES

NO

6.9

Section

15.6.

14.28g

Are the areas, where each one of the steps occur and the equipment utilized, indicated?

6.10

Section

14.23(f)

Are the procedures, or reference to them, applied to the preparation of equipment and their installations, indicated?

6.11

Sections

14.27 and

15.15

Are the areas and  equipment/ lines released recorded?

6.12

Are identification labels of areas and of equipment attached?

6.13

Sections

14.28c;

14.27 and

15.15

Is the date, the starting and ending time of every step recorded?

6.14

Sections

14.28(h) and

15.6

Are the values of operational deviations to be controlled during process (Ex.: temperature, pH, times, agitation speeds, etc.) recorded?

When it corresponds, are records attached?

6.15

Section

14.28(I).

Are the acceptance limits of such deviations indicated?

6.16

Section

14.28(g)

If there are process deviations with regard to the master formula, are they recorded?

6.16.1

Sections

14.28(j) and

15.3

Are they authorized by quality assurance personnel?

6.16.2

Section

15.3

Is the management of deviations undertaken as outlined in a SOP which has been previously established?

Ref.

32º WHO

BATCH PROCESS RECORD

YES

NO

6.17

Sections

15.2;

16.12 and

14.28(e)

Whenever Quality Control intervenes in some step of the process, are interventions recorded?

6.18

Sections

14.28 (I);

15.4 and

14.28(I)

Are the real yields of the intermediate and end stage recorded?

6.18.1

Sections

14.28 (I) and

15.4.

Are the yields within the acceptable limits?

6.18.2

Section

16.15.

In case of a deviation, is the cause of the deviation investigated according to the SOP?

6.18.3

Section

16.15.

Are the investigation findings documented?

6.19

Section

4.28(e).

14.28(j);

14.28(d) and

14,28(h)

Are the signatures/ initials of the people who carry out the different operations and of those who supervise them recorded?

6.20

It is verified that the data that should appear on the batch process record are completed at the time in which each action is undertaken during the process?

6.21

Is the reprocessing of products done in accordance with a SOP?

6.22

Are reprocessing and reworking previously authorized by Control/Quality Assurance?

7

Section

14.8

After the manufacture process is ended, is all the documentation that is part of the batch record, including the certificate of analysis of the Finished Product, filed?

Ref.

32º WHO

BATCH PROCESS RECORD

YES

NO

8

Section

14.8.

Is the file maintained for at least one year after the Expiry date of the lot?

9

Sections

14.38;

14.39 and

14.40.

Is a correlative/sequential and traceable record taken from each production?

Ref.

32º WHO

PACKAGING

YES

NO

10

Section

14.25

Are there instructions for product packaging, updated and authorized by the qualified person responsible and/or Quality Assurance/Control for each product, size of container and dosage form?

11

Section

14.25

Does the company have packaging orders with the following information:

11.1

Section

4.25(a).

Full name and code of the product?

11.2

Lot number?

11.3.

Section

14.25(b).

Presentation unit, dosage forms description and strength/potency?

11.4

Issue date?

11.5

Starting date?

11.6

Finishing date?

11.7

Expiry date and product shelf life for each batch?

11.8

Section

4.25(c).

Package size, regarding number, weight or product volume in the final container?

Ref.

32º WHO

PACKAGING

YES

NO

11.9

Section

14.25(d)

A full list of all packaging material required for a normal size batch, including quantities, sizes and types, with the lot number, code or reference number related to specifications for every packaging material?

11.10

Section

14.25(f)

Special precautions to be observed, including review of packaging area and equipment for release of production line, as well as, the cleaning requirements of the area and equipment?

11.11

Section

14.25(g).

A process description, including any important supplemental operations, and equipment to be used?

11.12

Section

14.25(h)

Details concerning process control with instructions for the sampling and acceptable limits?

11.13

Forms for recording product specifications during packaging process (check up process starting, sealing tests, bottle closures, filling volume, lot number, expiry date, etc.) done by packaging and quality control personnel?

11.14

Signature of the person responsible for the packaging operation?

11.15

Signature of the person who has dispatched packaging material and of the personnel who has verified this?

11.16

Signature of the person who has received packaging material?

11.17

Signature of the Quality Control inspector during the processes?

11.18

Yield of packaging operation?

11.19

Observations (space adequate to note any information or deviation)?

Ref.

32º WHO

BACTH PACKAGING RECORDS

YES

NO

12

Section

14.29.

Is a packaging order for every batch or part batch processed issued?

13

Section

14.29.

Does the packaging order conform to the packaging instructions?

14

Section

14.30

Is the release of areas and equipment/ lines recorded?

15

Sections

14.30 and

14.31

Are the signatures/initials of the people responsible for the different operations recorded?

16

Sections

14.30 and

14.31

Does the batch packaging record contain the following information:

16.1

Section

14.31(a)

The name of the product, the batch number and the quantity of bulk product to be packed, as well as the batch number and the planned quantity of the finished product that will be obtained, the quantity actually obtained, and the reconciliation?

16.2

Section

4.31(b).

The date (s) and time(s) of the packaging operations?

16.3

Section

14.31(g)

The expiry date of the finished product?

16.4

Section

14.31(c)

The name of the responsible person carrying out the packaging operation?

16.5

Section

14.31(d)

The initials of the operators of each one of the different steps?

16.6

Section

14.31(e)

The controls undertaken with the outcome of verifying the identity and conforming to the packaging instructions, including the results of the inprocess controls?

Ref.

32º WHO

BACTH PACKAGING RECORDS

YES

NO

16.7

Section

14.31(g)

14.31(f)

Details of the packaging operations carried out, including references to equipment and the packaging lines used, cleaning records?

16.8

Section

14.31(f)

If necessary, the instructions for keeping the product unpackaged or a record of returning product that has not been packaged to the storage areas?

16.9

Section

4.31(g).

Whenever possible, are samples of the printed packaging materials used, including samples bearing the batch number, expiry date and any additional overprinting kept?

16.10

Section

14.31(h).

Notes on any special problems, including details of any deviation from the packaging instructions, with written authorization by the qualified person responsible?

16.11

Section

14.31 (I)

The quantities and reference numbers or identification of all the printed packaging materials and bulk product issued, used, destroyed or returned to stock and the quantities of product obtained to permit an adequate reconciliation?

16.12

Section

14.31

Is there a check to ensure that the data that appears on the batch packaging records are completed at the moment that each action is carried out during

the process?

16.13

Sections

13.26; 14.31(h) and

15.3

Are the reprocessing and reworking of products controlled in a SOP for deviations?

16.14

Section 13.28.

15.3

Is the intervention of Quality Control included in this SOP?

Ref.

32º WHO

BACTH PACKAGING RECORDS

YES

NO

17

Section

14.8 and

14.9

After the packaging process is ended, is all the documentation that is part of the batch packaging record, including the analytical protocol of the Finished Product, filed?

18

Section

14.8

Is the file maintained for at least one year after the Batch expiry date?

19

Sections

14.38;

14.39;

14.40;

14.41 and

15.2

Is a correlative/ sequential and traceable record of each production or deviation kept?

Ref.

32º WHO

GENERAL DOCUMENTATION

YES

NO

20

Section

14.1.

All applicable SOPs are available in each area where they are required?

21

Section

14.4.

For each procedure, are the purpose, scope, references, and responsibilities

clearly defined?

22

Section

14.4.

Is there the detailed and precise description, in chronological order of the routine operations?

23

Sections

14.3 and

14.25.

Are the date issued and the effective date indicated?

24

Section

14.5

Are the procedures available, current?

25

Section

14.3.

Are the signatures of the personnel that issue, review, and approve the document indicated?

26

Section

14.8.

Are the records indicated within the procedures available?

Ref.

32º WHO

GENERAL DOCUMENTATION

YES

NO

27

Section

14.10

Are the labels adhered to containers, equipment, and other auxiliary elements of production and areas clear and unambiguous?

28

Section

15.6.

Do the labels indicate the condition in which products, equipment, and areas are found?

29

Section

14.7

Is the way in which data is amended due to writing errors defined?

29.1

Section

14.7.

Does the use of correction fluid or eraser remain clearly prohibited in the documentation?

29.2

Section

14.7 and

14.3

If there are amendments/changes, are the date and signature recorded?

30

Sections

14.5 and

15.3

Is there a SOP for the handling of changes and deviations?

31

Sections

14.38 and

14.41

Is there a written procedure outlining the combination of numbers and letters that form the identification of the lot, to ensure that it is safe and correct?