Essentials of Development Notebook for pharmaceuticals
The pharmaceutical Development Notebook is a critical component for the conception of new products. In addition, it is a fundamental requirement for successful pharmaceutical formulation development.
Characteristics of Development Notebook books
Each page and each piece of information is essential in the development book. Therefore, once the book is issued to scientists to develop a pharmaceutical formulation, none of the pages should be removed from the book, irrespective of circumstances.
For that reason, loose leaves and spiral-bound Development Notebook books must not be permitted for pharmaceutical development purposes.
The bounded Development Notebooks should have numbers on each page, and a total number of pages issued should be written on the first page.
Hardcover notebooks are appropriate for use and maintain development work for a more extended period. In addition, hardcover notebooks are ideal for a laboratory environment.
The development notebook is the critical document for preparing the development report, the basis for formulation submission to the agency, and the troubleshooting guide throughout the product life cycle.
Documentation in Development Notebook
In the development notebook, all the entries should be done in chronological order starting from page one to the last page of the notebook.
While entering the information, none of the pages should be left blank with the intent to make an entry at a later date.
All the entries should be done with the date and time for end-to-end traceability of information generated during the development work.
Issuance and control procedures are essential for oversight and control over development notebooks.
Each notebook should be daily (or periodic) audited and signed by the team leader or another scientist to ensure that laboratory notebooks are maintained up to date and in line with the organization’s expectations.
The purpose of the development notebooks is to document all pre-formulation and product development information.
Therefore, the record of all successes and failures in the experiment must be recorded.
In addition to the information regarding experiments, supporting information such as equipment and instrument printouts and chromatograms should be part of the development notebook. The printout should be attached to the notebook in such a way that it should not be able to remove from the notebook. The data should be pasted in such a way that it should not cover any experimental data or written information.
In case when data are in the form of electronic records, scientists should provide the reference number of the electronic record in the development notebook.
The thermal paper should not be used to print the raw data. However, if there is no other option, photocopies of thermal paper printouts should be maintained because the information from the thermal printout gets faded and removed over in the long run.
Printouts in the Development Notebooks should be signed by one person and verified by the supervisor.
Completed Development Notebook should be achieved in such a way that it should be readily retrieved as and when needed for reference.
Error correction should be done in the Development Notebook as per Good Documentation Practice Principles and ALCOA+ principles.
While carrying out essential activities and critical information recording, such as ingredient weighing, recording of in-process parameters, etc., should be done by one person and verified by a second person.
Typical information is recorded in the Development Notebooks are:
● Details of experiment
● Ingredient lot number
● Expiry dates
● Source of active and excipient (vendor or supplier)
● Analytical method and specification reference numbers
● Equipment and instrument numbers
● Equipment parameters
● In-process controls
● Recommendation on specification
● Critical Process Parameters
● Critical Quality Attributes
● Events and investigations and their conclusions
Other essential elements of documentation and Development Notebook
Instruments and equipment used to carry out the operation must be within the calibrated and qualified state
The development quality assurance department should review Development Notebook data. Procedure for review of the Development Notebook should be established.
A well-documented and controlled development operation reduces efforts and allows speedy drug development at the lowest cost.
Meticulous documentation of development work helps in the timely completion of development work and quick review. In addition, accurately recorded information will help in the long run throughout the product lifecycle.
The documentation and data reported in the Development Notebook are primary data to prepare the development report required for the product submission to the regulatory agency.
Some portion of time should be budgeted for the documentation and review of the Development Notebook to ensure adequacy and accuracy of data and to ensure compliance with the procedures and protocols.
Electronic Laboratory Notebooks or Electronic Development Notebooks
With help of technology, advancement is development and laboratory notebooks are possible. Development notebooks are available in the form of electronic application. The applications those are meeting the FDA’s CFR 21 Part 11, EU Annex 11 or GMP & GLP guidelines are reliable solutions to ensure the data integrity, easy to maintain and other many advantages.
Checklist or cheat sheet for Development Notebooks:
● Development Notebook must have bounded and with page numbers.
● Every page of the Development Notebook must be signed and verified by the team leader.
● Errors must be corrected as per Good Documentation Practice principles.
● All development work should be documented in chronological order without keeping blank pages in between.
● All the experiments must be documented, whether it is successful or not.
● All printouts and supporting information to be attached with the Development Notebook or referred to an appropriate traceable documents. It should not lose its identity and traceability over a period of time.
● Calculations and supporting attachments should be checked and signed by a second scientist to the team leader.
● All the activities must be in line with product development SOPs and Protocols.
● In-process data and tentative specifications must be documented.
● Appropriate critical upper and lower range limits should be challenged during the experiment.
● All investigations and events must be documented with appropriate root cause and outcome.
● Lot/ batch number of starting materials, manufacturing dates, expiration dates, source of active ingredient and excipient must be documented.
● A list and certificates of critical consumables should be maintained.
● A certificate of analysis of starting materials and components should be maintained.
● All the elements of the development report must be covered in the Development Notebook.
● The product Development Notebook comprises formulation development as well as analytical method development.
● Essential procedures for issuance and control of the Development Notebook should be established, such as
1. Issuance and use of pharmaceutical Development Notebook.
2. Review of Development Notebook.
3. SOP for generic product development.
4. Storage and archival of generic product Development Notebook.