Investigational Medicinal Product (IMPD) Guideline

Standard Operating Procedure (SOP) & Guideline for manufacturing, packaging (bulk and packed), labeling, testing, release, shipping, and destruction of Investigational Medicinal Product (IMPD Clinical Trial).

Investigational Medicinal Product (IMPD)

Investigational Medicinal Product (IMPD Clinical Trial)

1.0   PURPOSE:

    • To describe the procedure for the manufacturing, packaging, labeling, release, shipping, and destruction of Investigational Medicinal Product (IMPD).

2.0   SCOPE:

    • This procedure is applicable to the manufacturing, packaging (bulk and packed), labeling, testing, release, shipping, and destruction of Investigational Medicinal Product (IMPD) including placebo.
    • This procedure also includes drug products to be manufactured for different phases of Investigational Medicinal Product (IMPD) clinical trials including Bioavailability (BA/Bio Equivalence (BE) studies.
    • New chemical entity/New molecules/ innovative products are not under the scope of this guideline.

3.0   REFERENCES:

    • The following SOPs and Guidelines (linked below) have used as a reference during the preparation of this document.

4.0   RESPONSIBILITY:

    • Formulation Development (FDD)/Packaging Development Department (PDD):

    • Master Formula preparation and release, and wherever applicable preparation of artworks and related documentation.
    • MPS/PMD approval of drug product and packaging and artwork initiation work with coordination of PDD.
    • Head Production:

    • Ensure all equipment; utilities and facilities are in their current state of qualification and calibration, procurement of machine change parts, creation / up-gradation of the facility.
    • Work Order creation and preparation of masterbatch manufacturing records.
    • The Head – Engineering & Quality Assurance:

    • Qualification, Creation/up-gradation of facility and equipment.
    • Ensure all equipment, utilities, and facilities are in their current state of qualification and calibration of the QC instrument.
    • The Head – Analytical Development (ADD) and Quality control :

    • Ensuring the availability of required-
      • Specifications,
      • Testing Procedures,
      • Chemicals,
      • Other Analytical Requirements,
      • Arranging for sampling & testing of materials required in the manufacturing/ packaging of Investigational Medicinal Product (IMPD),
      • Testing and release of in-process samples and finished goods samples related to the Investigational Medicinal Product (IMPD).
    • The Head Quality Assurance (QA):

    • Application to State Food Drug Administration for a manufacturing license.
    • Masterbatch record approval,
    • Cleaning validation of manufacturing equipment,
    • Arranging for a sampling of in-process & Finished goods,
    • Collections of control samples and stability samples (wherever applicable),
    • Ensure availability of specification and testing procedures – Cleaning validation matrix updating testing and approval of materials.
    • Ensuring GMP compliance during manufacturing and the release of Investigational Medicinal Product (IMPD) batches from the site.
    • Investigations into complaints related to Investigational Medicinal Product (IMPD) and ensuring implementation of necessary corrective actions. head QA is also responsible for recommending recall of Investigational Medicinal Product (IMPD) batches whenever required.
    • Scientist of Formulation Development Department :

    • Providing all the information required for the manufacturing, testing, and storage of Investigational Medicinal Product (IMPD) as MPS/PMD and Technical Data Package.
    • Appropriate and required training of site personnel with respect to safe & appropriate handling/ storage and destruction of Investigational Medicinal Product (IMPD).
    • Providing the required specifications, testing procedures, TDPs (wherever applicable), technical inputs necessary for handling/ manufacturing/ testing/packaging.
    • Providing a rationale for cleaning validation acceptance criteria, the method for cleaning validation, technical help to carry out the cleaning validation whenever required.
    • The arrangement of stability studies (whenever required); co-ordination with other R &D groups for carrying out clinical studies, etc.

5.0   PROCEDURE FOR INVESTIGATIONAL MEDICINAL PRODUCT (IMPD):

  • Part: A When Investigational Medicinal product (IMPD) is manufactured as a Clinical Trial /Submission Batch or scale-up batch for stability and regulatory filing purpose.

    • If the Investigational Medicinal Product (IMPD) happens to be a Clinical Trial /submission batch or scale-up batch, all the systems & SOPs related to the manufacturing of scale-up/ Clinical Trial/Submission Batches shall be applicable.
    • FDD/ADD shall provide all the necessary documentary & technical support for manufacturing, testing, and storage procedures of the drug product and their components that are related to the Investigational Medicinal Product (IMPD).
    • Such documentary/ technical support shall include all related,

      • Specifications,
      • Test procedures,
      • Cleaning Methods,
      • Cleaning Validation Analytical Methods,
      • Material Safety Data Sheet (MSDS),
      • TTD (Technology Transfer Documents).
      • Drug Product Manufacturing Procedure,
      • Drug Product Packaging Details,
      • Artwork Details, and
      • Storage conditions required for the Drug product and its components.
    • ADD shall provide specific chemicals, reference standards, and/or Working standards/HPLC Columns and any other analytical support whenever required for the analysis of such drug product and its components.
    • FDD/ADD shall share all information and relevant documents to the QA representative responsible for the project at the site.
    • Formulation Development Team shall provide adequate training information with respect to the specific requirements if any to the Personnel involved in the manufacturing, handling, testing, and storage of Investigational Medicinal Product (IMPD) and their components.
    • FDD/Regulatory Affairs Team shall provide the details of manufacturing NOC/DL to the Head QA for obtaining the license to manufacture drugs for purpose of examination, test, or analysis from licensing authorities.
    • The availability of the license shall be ensured by HOD QA, before initiating manufacturing activity.

    • The introduction of IMPD/placebo at site/manufacturing location shall be evaluated as per the SOP on Change Control Management.
    • Based on the technical data package, FDD will take up the scale-up or feasibility trials for the process parameters, batch size fixation as per the respective SOP Batch Size Determination.
    • After receiving the required details Production / QA prepares the BOM, Master Batch Production Records, or related SOPs if any, and get them reviewed and approved by all concerned.
    • The Manager- Production / FDD and QC shall ensure that all the equipment/ Instruments, Utilities, and Facilities are in their current state of qualification and Calibration. Any New Equipment / Instruments, Utilities, and Facilities shall be qualified before use.
    • All the related drug substances shall be tested as per the relevant specifications and released before starting manufacturing.
    • All the testing in the Quality Control laboratory shall be done using respective test specifications & test procedures.

    • If the Investigational Medicinal Product (IMPD) is a scale-up/or a Clinical Trial/Submission Batch, the acceptance limits for cleaning validation shall be decided as per (respective Cleaning validation protocol) and compliance to the same shall be ensured before giving line clearance.
    • All the operations shall be carried out by trained personnel as per the approved and authorized written procedures with due line clearances at the appropriate step.
    • All the retention and stability samples shall be withdrawn as per approved SOPs and Charged at the site or sent to FDD as per the decision with respect to that particular product. (Refer respective SOP) for samples related to CT/Submission Batches)
    • Any Deviations from the written procedures shall be handled through the (Respective SOP for Incidents/Deviation)
    • All process deviations shall be duly justified/supported, investigated, and documented.
    • The executed Batch Production Records, Analytical Data, and any related deviation or investigations (if any), etc. shall be reviewed by the Quality Assurance Department.
    • If an Investigational Medicinal Product (IMPD) is a Clinical Trial/Submission Batch, then the related documents shall be stored forever.
  • Part B: When Investigational Medicinal Product (IMPD) is manufactured for Bioavailability/Bio Equivalence or clinical trial purpose:

    • If an Investigational Medicinal Product (IMPD) is manufactured for BA/BE or clinical trial purpose then FDD will send an order or request form. Refer to Annexure 1.
    • The same shall be attached to the executed batch production record.
    • Introduction of Investigational Medicinal Product (IMPD)/placebo at site/manufacturing location shall be evaluated as per the SOP on Change Control Management and SOP for the introduction of new Products.
    • When initially no information is available whether the batch will go for bio-equivalence or not, order details will be included as a part of BPR as and when required/ applied.
    • PTD/PTT shall provide the details of manufacturing to Head production for obtaining the manufacturing license from licensing authorities.
    • FDD shall provide all the information required for the manufacturing, testing, and storage of Investigational Medicinal Product (IMPD) as TTD (Technology transfer dossier) e.g.,
      • Manufacturing Formula & Process for the formulation & packaging,
      • Specifications & Test methods of Raw Materials/ Packaging Materials & Finished Product,
      • Stability data & Protocol, labeling & packaging requirements for the study.
    • The information /documents shall include the below:

      • Specifications and analytical methods for starting materials, packaging materials, intermediate, semi-finished, and finished products.
      • Manufacturing methods.
      • In-process testing and methods
      • Approved label copy
      • Relevant clinical trial protocols and randomization codes, as appropriate.
      • Relevant technical agreements with the contract givers/sponsor, as appropriate.
      • Stability data
      • Storage and shipment conditions
      • MSDS
      • Randomization codes
      • Any special instructions, if any.
    • The contents of the information may vary depending on the product and stage of the development.
    • In the event of any revision / updation, revised MPS / PMD shall also be shared by FDD /PDD respectively.
    • QA shall ensure the availability of required Technical agreements with ‘Clinical Trial Sponsor’ and relevant authority.
    • This shall address compliance of product Produced with clinical trial authorization.
    • It will also include a certificate of compliance issued by plant QA stating that the product is meeting applicable regulatory requirements.
    • Validated cleaning method shall also be provided by FDD.

    • The acceptable limits for cleaning validation shall be decided by the FDD in consultation with QA considering safety, toxicity e.g. NOEL, etc.
    • Cleaning processes shall be defined e.g., type of solvents to be used, type of cleaning, the time between the end of production, and cleaning.
    • The manufacturing of the placebo shall be done only when the absence of the contaminant is proven.
    • In the case of highly potent molecules, to ensure the absence of trace amount of the drug product or its component from the manufacturing equipment, which is beyond the normal controls applied at the location, the specific validated analytical method is required to be provided by R & D to detect such subnormal levels of the active entity.
    • The same shall be applied to check the cleanliness of equipment before undertaking to manufacture of the next product.
    • FDD shall ensure training in accordance with written programs for all personnel involved in manufacturing, handling, and packaging including blinding, testing, storage, and shipping.
    • Head manufacturing, Head PTD/PTT, and Head QA shall ensure adequacy with respect to Premises and equipment for the manufacture and packaging of IMPD and shall ensure that all the equipment/instruments, facilities are qualified before use.
    • In case the Drug Product or its components are required to be specifically treated before disposal, due to any safety concerns, the method for the same shall be shared by FDD/ADD.
    • Proper records shall be maintained for this activity.

    • Production / QA shall prepare the master formula, BPRs, packaging instructions, and storage & Shipping instructions on the basis of order received from FDD.
    • Instructions shall include the sample required to carry out quality control testing, reference, and retention samples.
    • Reconciliation should be carried out at each stage of processing.
    • All the related drug product components shall be tested as per the approved specifications and released before starting the manufacturing.
    • All the testing shall be done in the Quality control laboratory as per the approved specifications using all necessary precautions suggested in the Standard Test Procedure.
    • All the retention and stability samples shall be withdrawn as per approved SOPs and stored at the location or sent to R & D as per the decision with respect to that particular product.
    • The reconciliation shall be carried out thoroughly after the packing of the product.
    • For the packaging of supplies for blinded clinical trials, line clearance shall be given by QA at each step as per the documented plan prepared before the start of the activity.
    • The plan shall include the precautions to be taken to avoid mix-ups of the product during the packaging.
    • The plan shall be signed by the designated packaging and QA personnel.

    • Investigational Medicinal Product (IMPD) shall be packaged in similar packs subject wise for each center as per the randomization schedule.
    • The randomization schedule shall be received from the FDD kept in a sealed envelope until packaging operation starts and shall be kept confidential.
    • De-coding if required shall be done as per the SOPs of the respective department of FDD for the purpose and arrangements shall be made by the clinical operations team to make the required documents available at the investigator site.
    • The investigational product(s) [including active comparator(s) and placebo, if applicable] shall be coded and labeled in a manner that protects the blinding.
    • The labels for packaging of samples to be used for clinical trials shall be generated as per the information received from FDD and shall contain the following minimum information.

    • A statement “for clinical trial use only-not for sale”$ or similar wordings
    • Generic name/product code
    • Quantity/units in one pack
    • Study number
    • Sub number/identification number which will be the same randomization number (if applicable)
    • Date.
    • Date (Period of use (use-by-date, expiry date or re-test date as applicable), in month/year format and in a manner that avoids any ambiguity).
    • Batch No. (The batch and/or code number to identify the contents and packaging operation).
    • Code number (for open-label/single-blind studies) (A trial reference code allowing identification of the trial, site, investigator, and sponsor if not given elsewhere).
    • Storage instruction / Conditions
    • The instruction “Keep out of reach of children” except when the product is for use in trials where the product is not taken home by subjects.
    • Warning if applicable any
    • Manufacturer name and address
    • Name of sponsor
    • Visit number if applicable for single studies
    • Name, address, and telephone number of the sponsor, contract research organization, or investigator (the main contact for information on the product, clinical trial, and emergency unblinding).
    • Pharmaceutical dosage form, route of administration, the number of dosage units, and in the case of open trials, the name/ identifier, and strength/potency.
    • The batch and/or code number to identify the contents and packaging operation.
    • A trial reference code allowing identification of the trial, site, investigator, and sponsor if not given elsewhere.
    • The trial subject identification number/treatment number and where relevant, the visit number.
    • Directions for use (reference may be made to a leaflet or other explanatory document intended for the trial subject or person administering the product).
    • Applicable in case the product to be used in clinical trial purposes.

    • An approved label with the above contents shall be received from the respective department of FDD.
    • The format of the label shall be as mentioned in Annexure –2, 3 & 4.
    • In case expiry dates are to be changed, an additional label shall be affixed indicating the expiry date.
    • This shall be done at the manufacturing site with proper controls like QA check or at the investigator’s site under the supervision of the pharmacist.
    • This additional labeling shall be documented in both the trial documentation and in the batch records.
    • In case matching comparators (drug/placebo) are used for blinding, then it must be ensured that the test and the comparator medications can not be distinguished (appearance, taste, color, size, shape, smell, consistency, texture, etc.) from each other before or during administration.
    • Packaging of trial medication shall be done in such a way that the test drug is not distinguishable from the comparator (drug/placebo) in terms of features including but not limited to the expiry date of study medications, type of packs, and label design.
    • When two medications to be administered in a blinded clinical trial have different expiry dates, then the earlier of the two expiry dates shall be printed on the labels of both medications packages.
    • Quality control shall be performed as per the documented plan prepared before the start of the packaging activity so as to ensure that blinding is maintained.
    • Retention and reference samples shall be stored at the respective department of FDD sending the request for manufacturing.
    • The duration and the conditions maintained shall be as per the SOPs of the respective departments.
    • Each batch shall be assessed prior to release by QA.
    • This shall include:

    • Batch records, including control reports,
    • In-process test reports and release reports.
    • Compliance with the product specification file,
    • The order, protocol, and randomization code.
    • All records duly signed by authorized personnel including planned changes and deviations.
    • Production conditions
    • Validation status of facilities, processes, and methods
    • Examination of finished packs
    • Stability reports
    • Source and verification of conditions of storage and shipment
    • Self-inspection reports/audit reports for verification of the quality system of the site
    • Ensure verification and compliance to GMP and respective regulatory requirements
    • Documents certifying that the location is authorized to manufacture Investigational Medicinal Product (IMPD) or comparators for export by the appropriate authorities in the country of export.
    • Provide certification of compliance to relevant authorities that the product has been manufactured in compliance to GMP procedure and as per respective regulatory requirements.
    • Shipping of the trial medication:

    • Ship in a controlled manner as per the shipping order and data loggers shall be used during transit.
    • In case a transfer of Investigational Medicinal Product (IMPD) is required from one site to another, it shall be done as per the relevant SOPs of the respective departments of FDD responsible for conducting the trial.
    • Complaint handling, recalls, and returns shall be done as per the current version of the SOPs on complaint handling, Recall Procedure, and Returned at manufacturing location for the same as per SOP.
    • Archiving:
    • All Retention and reference samples including blinded products shall be kept for at least two years after completion of formal discontinuation of the last clinical trial in which the batch was used, whichever period is longer Batch Production Records shall be retained forever after the completion of formal discontinuation of the clinical trial as informed by FDD or as per Technical agreement whichever is longer.
  • Deactivation Procedure of Investigational Medicinal Product:

    • General Instruction:

    • Use personal protective equipment during handling of hormone material
    • Prepare the 10% Sodium Hypo-chlorite solution as per the requirement of the day.
    • Deactivation procedure for Non-Recovery:

    • Collect all the recoveries generated during dispensing, granulation, compression, coating, and packing in a container and affix the non-recovery label and mention “Ready for disposal” in the label.
    • Transfer the container to the washing area.
    • Add a sufficient amount of 10% Sodium Hypo-chlorite solution to completely immerse the material and keep for 15 minutes.
    • Stir slowly to convert the material into slurry form.
    • Send it to ETP/STP for disposal.
    • The containers used for deactivation of non-recoveries shall also be deactivated by using a 10% Sodium Hypochlorite solution.
    • Deactivation procedure for the used disposable materials:

    • Collect all the disposable materials like nose, mask, gloves, shoe covers, used polybags, etc. in a container.
    • Keep this for about 15 minutes for deactivation.
    • Drain the solution and collect it in a container.
    • Rinse with water twice and then collect it in the same container.
    • The collected solution shall be sent to ETP for disposal.
    • Deactivation procedure for the used gowns :

    • Collect all the used gowns in a container in the washing area.
    • Dip all the gowns in potable water for around 30 minutes and then rub the gowns properly, so that all the dust particles come out to the water.
    • Then drain out the water and collect it in another container.
    • Add a 10% Sodium hypochlorite solution to the collected water.
    • Keep for 15 minutes.
    • Send the collected solution for disposal in ETP.
    • Then send the gowns for washing and drying.
    • Deactivation procedure for the leftover samples of QC :

    • Collect all the QC leftover samples in a container after completion of the analysis.
    • Dip all the leftover samples in 10% Sodium Hypochlorite solution for 15 minutes.
    • Make slurry and send it to ETP for disposal.
    • Deactivation procedure for engineering non-recoveries :

    • Collect all the non-recoveries from AHUs, Dust Extractors, etc. in a container.
    • Add a sufficient amount of 10% Sodium Hypochlorite solution to completely immerse the non-recovery material and keep for 15 minutes.
    • Make slurry and send it to ETP for disposal.
    • Procedure for Returned Investigational Medicinal Product for Clinical supplies

    • The clinical research team will intimate before the dispatch of clinical supplies from sites.
    • After receiving the returned clinical supplies, designated plant personnel to verify the returned clinical supplies against the information provided by the clinical research team to check the quantity and other details of returned materials.
    • Designated personnel to Open the shipment and check that supplies are as per information provided by the clinical research team and note down the details in the Investigational Medicinal Product (IMPD) return receipt log.
    • Document the discrepancies (if any) in the comments section of the “Investigational Medicinal Product return receipt log” as per Annexure 8.
    • Verify the condition of packed materials and ensure the returned can be safely handled.
    • If the returns cannot be safely handled then inform the clinical team and follow the instruction.
    • After verification, Sign and Date the “IMPD return receipt log” and document in the respective BPR.
    • Store the returned materials in respective storage areas with specific labeling in the return package.
    • Wait till further instruction from the clinical research team to handle the returned clinical supplies.
    • Destruction of the Investigational Medicinal Product (IMPD) :

    • The clinical research team will intimate for the destruction of the returned and/or unused Investigational Medicinal Product for clinical supplies and other study-related supplies.
    • After receiving the written clinical supplies destruction details from the clinical research team, designated plant personnel to verify the destruction information to check the details of materials to be destructed and document the details in the ‘‘Investigational Medicinal Product (IMPD) Destruction checklist’’ as per Annexure 9.
    • Collect the materials from the respective area for destruction.
    • After completion of the expiry date of the clinical trial batch sample, QA shall prepare the letter and sent it to the local FDA for the destruction of the available sample at the site.
    • On the completion of the destruction of clinical supplies, acknowledge the destruction details to the clinical research team
    • Attach the document of the destruction details in the respective BPR.

6.0   ABBREVIATIONS – INVESTIGATIONAL MEDICINAL PRODUCT (IMPD):

Word

Abbreviations Word

Abbreviations

ADD: Analytical Development Department AHU: Air Handling Unit
BA: Bioavailability BE: Bio Equivalence
BMR: Batch Manufacturing Record BOM: Bill Of Material
BPR: Batch Packing Record CCR: Change Control Record
CRD: Clinical Research Department CT: Clinical trial
DL: Draft Label ETP: Effluent Treatment Plant
FDA: Food Drug Administration FDD: Formulation Development Department
GMP: Good Manufacturing Practices IRA: Indian Regulatory Affairs
IMPD: Investigational Medicinal Product NOC: No Objection Certificate
MSDS: Material Safety Data Sheet NRR: Non-Recoverable Recovery
NOEL: No Observe Effect Level PTT: Process Technology Transfer
PTD: Product Technology Development TTD: Technology Transfer Dossier
  • Definition of Terms – 

Term

Definition

Blinding:

  • A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s).
  • Single-blinding usually refers to the subject(s) being unaware, and double-blinding usually refers to the subject(s), the investigator (s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s).
  • In relation to an investigational medicinal product, blinding shall mean the deliberate disguising shall mean the disclosure of the identity of a blinded product.

Common types of Study

 

  • Open-Label: The subjects involved in the study and the investigator know which study treatment they receive.
  • Single Blind Study: The subjects involved in the study do not know which study treatment they receive.
  • Double-Blind Study: Both subjects and researchers do not know which treatment is being given to any given subject. A form of double-blind study called a “double-dummy” design allows additional insurance against bias or placebo effect. In this kind of study, all patients are given both placebo and active doses in alternating periods of time during the study.

Investigational Medicinal Product (IMPD):

  • A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the authorized form, or when used for an unauthorized indication, or when used to gain further information about the authorized form.

Randomization:

  • The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments to reduce bias.

Sponsor:

  • An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial

Product specification file:

  • A reference file containing or referring to files containing, all the information necessary to draft the detailed written instructions on processing, packaging, quality control testing, batch release, and shipping of an investigational medicinal product

Investigator:

  • A person is responsible for the conduct of the clinical trial at a trial site.
  • If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and maybe called the principal investigator

Retention sample:

  • A sample of a batch of starting material, packaging material, the product contained in its primary packaging, or the finished product which is stored for the purpose of being analyzed should the need arise.
  • Where stability permits, reference samples from critical intermediates stages (e.g. those requiring analytical testing and release) or intermediates that are transported outside of the manufacturer’s control should be kept.

Reference sample:

  • A sample of a packaged unit from a batch of the finished product for each packaging run/trial period.
  • It is stored for identification purposes.
  • For example, presentation, packaging, labeling, leaflet, batch number, expiry date should the needed arise

Test Batch:

  • It is a batch of finished drug product manufactured according to cGMP regulations in support of regulatory approval or it is a batch manufactured prior to validation, which is a base on which an application is approved

CT/Submission batch:

  • This refers to any batch submitted in support of regulatory approval which includes bio-equivalence, test, and clinical trial report of a drug product.
De labeling:
  • De labeling is a process by which rejected labels removed from Bottles/Show boxes etc.
Re Labelling:
  • Re labeling is a process by which Bottles/Show boxes etc. are re-labeled with the respective label
Returned Clinical supplies:
  • All Investigational product (IP) for Clinical supplies that are returned from clinical sites.
Unused Investigational Product
  • Investigational Product which was packed for clinical supplies, but was not supplied to sites and remain at the plant as unused

7.0   ANNEXURES –INVESTIGATIONAL MEDICINAL PRODUCT (IMPD):

Annexure 1: Investigational Medicinal Product (IMPD) Request Form

Request Date: The drugs listed below are requested for use of:

Short study title:________________

Study number_______________

 

Protocol Summary enclosed:

Yes □      No    □

 

DD

 

MM

 

YY

If no instructions for formulation

as required by the study protocol:

  • Single-blind study
  • Double or Triple blind study
  • Double or □ Triple blind including dummies
  • Open non-comparative study
  • Others, Please specify_________
Date needed by :

 

 

 

DD

 

 

MM

 

YY

Clinical trial investigational product request from (Department) :

□ PDR    □ NDDS    □  NDDR   □ Purchase □ Others (Please specify __________)

Contact person and address to whom request is made : ___________________

Contact person and address to whom request to be sent:__________________

Shipping conditions :

Mode of transportation :

 

S. No. Name of Drug Label text enclosed Dosage form Strength Total units required Type of primary pack Units per primary pack Type of II

pack

Units per secondary pack Total no. of packs required
Requested by [__|__] [__|__]   [__|__]

DD        MM       YY

Approved by [__|__] [__|__]   [__|__]

DD        MM       YY

Annexure 2: Format of Label for Bio-equivalence studies when the product is to be subjected to clinical trials

SAMPLES FOR CLINICAL TRIAL USE ONLY

 NOT FOR SALE

STUDY NUMBER

SUB NO./IDENTIFICATION NO.

TRIAL REFERENCE CODE:

TRIAL SUBJECT IDENTIFICATION NO:

KEEP OUT OF REACH OF CHILDREN MEDICINE OUT OF REACH AND SIGHT OF CHILDREN VISIT NO. (2) NUMBER OF TABLETS/CAPSULES:
GENERIC NAME /STRENGTH /DOSAGE FORM/ROUTE OF ADMINISTRATION  STORAGE INSTRUCTION/CONDITIONS
SUBJECT NO. / IDENTIFICATION NO.
BATCH NO:

CODE NO.

MFG. DATE:

EXPIRY DATE:

DIRECTIONS FOR USE:
NAME OF THE SPONSOR:
WARNING (IF APPLICABLE):
MANUFACTURED BY/(NAME & ADDRESS )

Annexure 3: Format of the label for the stability studies.

SAMPLES FOR STABILITY STUDIES. (NOT FOR SALE)  
GENERIC NAME /STRENGTH /DOSAGE FORM STORAGE INSTRUCTION:
DIRECTIONS FOR USE: BATCH NO.: 

MFG. DATE:

EXPIRY DATE:

WARNING (IF APPLICABLE):
MANUFACTURED BY:

Annexure 4: Format of the label for the stability studies and Bioequivalence studies.

SAMPLES FOR STABILITY AND BIO-EQUIVALENCE STUDIES. (NOT FOR SALE)  
GENERIC NAME /STRENGTH /DOSAGE FORM STORAGE INSTRUCTION:
DIRECTIONS FOR USE:  Batch No: 

Mfg. Date:

Expiry Date:

Warning (If applicable):
Manufactured By:

Annexure 5: Investigational Medicinal Product (IMPD) Shipment Checklist

Study/Protocol No:
Address and contact details matching with the shipment request form (Yes/No):
Kit/Randomization  No. matching with the shipment request form (Yes/No):
Additional pack requirement included with the shipment  as per the shipment request form (Yes/No)
Documents requirement included as per the shipment request (Yes/No)
Proper packing to avoid any damage/movement within the outer box (Yes/No)
Placement of the data logger in the appropriate position (Yes/No)
The proper shipper arrangement by the designated courier  as per the transportation temperature conditions (Yes/No)
Specify the number of the box(es) per site
Shipment is handed over to the designated courier (Yes/No)
Comments (If any)

Annexure 6: Expiry Date Extension / Re-Labelling Request Form

Filled by Clinical Trial Team

Study/Protocol No:  
Version No./Date:  
Amendment No./Date:  
Study Title:  
Study Types (Open/Blind):  
No. of Treatment arms:  
Item Notes
Reason for Re-labelling
Kit Configuration
Current Expiry/Retest Date on the label
Current Batch No. on the label
Position of the new label/s on the Kit (pictorial views)
Any special label requirement (Opaque/Color label)
Quantity of Kits/units to be re-labeled at the plant:
Re-labeled kits to be ready at the plant by (Date):
Any Specific requirement

 

Filled by Formulation Development Department (FDD)

Study/Protocol No:  
Item Notes
New CoA available to update the Expiry/Retest Date for the same Batch Number:  
Current Expiry/Retest Date on the Label:  
New Expiry/Retest Date on the Label:

Specify the New Expiry/Retest date (as required):

A) Across all treatment arms for blinded labels B) Specific treatment arms for Open-label

 
New Artwork information provided to the Packing Development dept. (For each label type): Yes/No  
Quantity of labels required at the plant (for each label type):  
Quantity of labels required at depot/sites (for each label type):  
Any Specific requirement:  

Annexure 7: De-labelling and Re-labelling Form.

Packing Date: __________

Product Name: _________________________ Batch No._______________

De labeling Procedure:

  1. Remove the label from a plastic bottle with help of clean water.
  2. Remove the label from the corrugated box manually.

Performed By: ___________

100% Visual inspection of de-labeled components for Cleanliness

Visually inspection done by: _____________

After visual inspection of de-labelling procedure Total No. of de labeled units___________

Cleanliness of de-labeled components randomly Checked By packing Officer__________.

Verify by QA officer: ___________

Re Labelling Procedure:

After completion of the batch, labeling/ packing operation manually Preferably Pack these labeled Show boxes/Bottles in the identified boxes.

IPQA: Perform In process checks and documented during the relabeling procedure.

Labelling / Packing start on date: _____________Time:___________ Operator: _________

In-process control “X” mark means nil defects.
Inspection date
Inspection time
Defects
Product Identification
Defected Seal, cracked-punctured de-shaped.
Label Defective printing, text missing, improper sticking, dirty.
Wrong/Missing Mfg. Lic. No., Batch No, Mfg.Dt, Exp.Dt., Reg. No., NDC code, M.R.P (Whichever applicable)
Packed Case No./ Shipper No.

Annexure 8: Investigational Medicinal Product (IMPD) Return Receipt Log.

Filled by sponsor representative

Study/Protocol No.  
IMP Name  
Site No./ Investigator Name /Address  
IMP name and number Quantity Number of boxes Batch No.
Total     ———
Comments  

Annexure 9: Investigational Medicinal Product (IMPD) Destruction Check List.

Study/Protocol No:
IMP Name:
Batch No. of IP to be destructed:
Check and document the Study medication No/Kit No. of IP.
Quantities of IP (No. of Tablets/capsules/bottles/ vials/Pens):
Other Study Materials details (If applicable)
Date of Destruction:
Place of Destruction:
Comments:

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pharmabeginers

Janki Singh is experienced in Pharmaceuticals, author and founder of Pharma Beginners, an ultimate pharmaceutical blogging platform. Email: [email protected]

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