Procedure for change control in pharmaceuticals

Procedure for change control in pharmaceuticals

1.0         Purpose:

To
describe a procedure for change control.

2.0         Scope:

This
SOP shall be applicable for the identification, documentation, appropriate
review and approval of changes in raw materials, specifications, analytical
methods, facilities, support systems, equipment (including computer hardware)
processing steps, labeling and packaging materials, and computer software.

3.0         Responsibility:

Designee of Originating
Department:         

4.0         Procedure:

1.          The
initiating department shall initiate the change as per the change control
format no.

2.          The
initiating department shall furnish the details very clearly in the form for
present process/use, proposed change, Justification & impact analysis and
acceptance criteria.

3.          The
initiating department shall also define changes as major or minor based on
product quality or its impact of safety, health and environmental aspects. Some
of the major and minor changes are listed below: -

3.1       
Major Changes

For a substance of
chemical and microbiological quality evaluation.

•         Addition or
deletion of a step or addition of an alternative/new step in the formulation
manufacturing process.

•         Addition of a new
manufacturing site with modification of the formulation manufacturing process
described in the original dossier/document.

•         Change in input
quantities of formulation manufacturing process.

•         Changes in the
quality of raw material(s) or key intermediate(s) used in the formulation
manufacturing process.

 

3.2.   
Minor Changes

•        
Change in the administrative references (name/company name, address) of the
certificate holder.

•         Change in the
references (name/company name, address) of the manufacturing site.

•         Change or updating
of the methods of analysis used to test the substance.

•         Change in the
specifications of the substance.

•         Change in supplier
of starting and packing material.

•         Change in the batch
size.

•         Addition of a
new manufacturing site in the same site as described in the original dossier.

•         Change in the
documents like SOPs etc.

4.          The
Initiating department shall forward the proposal as per the requirement
to Formulation & Development Department for comments and clearance.

5.          After
giving comments/clearance, Formulation & Development shall forward the
change control form to Quality assurance department.

6.          On
receipt of Change control form from F & D department, QA shall assign the
Change control number as per the procedure given below:

                      Assigning
a change control number

      Each change
control number contains seven digits.

-     First two digits
represents change control code.

-     Third, forth and
fifth digit represent sequential change control No. (001 to 999)

-     Sixth and seventh
digit represents last two digits of the current year. (e.g.01,
02, 03…...99).

For
example, following change control no is decoded as explained.

CC-001/ 03.

CC = Change control code.

001=
Sequential Change control Number (001, 002, 003…………..999). 

03=
Current year 2003 (Last two digit of current year)

 

7.          QA
shall enter the details of Change in the Change control register.

8.          QA
shall evaluate the feasibility of the change and forward the change control
form to Regulatory affairs, if required.

9.          Regulatory
affairs shall evaluate the change in terms of any need to inform customer or
any updation in dossiers etc. and forward the change
to Site Quality Head.

10.      Site
Quality Head shall receive the comment form all the concerns and takes the
decision of approving or rejecting the change.

11.      On
completion of the total procedure, QA shall formally enter the status in Change
control Register and close the Change control Procedure.

12.      Put the
stamp of ‘OBSOLATE COPY’ on the old documents, where every this change control
procedure is applicable.

 

5.0      

Revision Log:

 

Revision No.	Effective Date	Reason
01	15.04.05	Format Changed

  
        

6.0                    Abbreviations:

Abbreviation	Expanded Form
QA	Quality Assurance
VP	Vice President
SOP	Standard Operating Procedure
F & D	Formulation & Development

7.0         

Annexure:

              
Annexure-1:      Change Control Form

 

 

       
                                                              Annexure-1

                                                              
Change Control Form

1.	Initiating Dept
	Change Control No.
	Stage/Document
	Manufacturing Date
	Implementation Date
2.	Present Process/Use*	Modification: Major/Minor
3.	Proposed Process/Use*
4.	Justification/Impact of Change*
5.	Supporting Data(If Required)	Enclosed/Not Enclosed
6.	Accepted Crieteria
7.	Signature: ________________                          ___________________                        (Officer/Executive/Designee)            (Head – Initiating Department)                    Date: _________________                         ____________________

 

8.	Comments from F&D Department*(if required)
				Modification:	Major/Minor
				Date:
	Signature	Manager-F&D
9.	Comments from Quality Assurance Department*
				Modification:	Major/Minor
	Regulatory Notification / approval			Required / Not Required
	Type of analysis to be carried out (if any extra analysis is required, give details):
	Subsequent Stages	Will be controlled/Not controlled
	Validation Status	Will affected / not affected
				Date:
	Signature	Manager - QA
10.	Comments from Regulatory Affairs Department*(if required)
	Proposed Change is recommended/ Not recommended
				Date:
	Signature	Manager – RA
11.	Comments from Engineering Department* (If required)
				Date:
	Signature	Manager - Engineering
12.	Comments
				Authorised / Not authorised
				Date:
	Signature:     Plant Head		Site Quality Head
*Whenever applicable, append supporting documentation.

                                                                      

  

 

Change Control Record

 

S.N	Date	Change Control no.	Originating Dept	Product / Document	Stage	Details of Change	Date of Implementation	Status	Remarks

 

Clinical Trials

Clinical Trials Introduction Clinical trials are a means of developing new treatments and medications for diseases and conditions. There are strict rules for clinical trials, which are monitored by the National Institutes of Health and the U.S Food and Drug Administration. Clinical trials are also called clinical studies, research protocols or medical research and often compare one drug against another to see which is more effective, or the medicine or procedure in a specific demographic group or for a specific disease. About Clinical Trials Why Participate in a Clinical Trial? Participants in clinical trials can play a more active role in their health care, gain access to new research treatments before they are widely available and help others by contributing to medical research. Where Do the Ideas for Trials Come from? Ideas for clinical trials usually come from researchers. After researchers test new therapies or procedures in the laboratory and/or in animal studies, the treatments with the most promising test results are moved into clinical trials. During a trial, more and more information is gained about a new treatment, its risks and how well it may or may not work. Who Sponsors Clinical Trials? Clinical trials are sponsored or funded by a variety of organizations or individuals such as physicians, medical institutions, foundations, voluntary medical-related groups and pharmaceutical companies, in addition to federal agencies such as the National Institutes of Health, the Department of Defense and the Department of Veteran’s Affairs. Trials can take place in a variety of locations, such as hospitals, universities, doctors’ offices or community clinics. What is a Protocol? A protocol is a study plan on which all clinical trials are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people can participate in the trial; the schedule of tests, procedures, medications and dosages; and the length of the study. While in clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment. What is a Placebo? A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment’s effectiveness. In some studies, the participants in the control group will receive a placebo instead of an active drug or treatment. What is a Control or Control Group? A control is the standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo. What are the Different Types of Clinical Trials? Treatment trials test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy. Prevention trials look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicine, vitamins, vaccines, minerals or lifestyle changes. Screening trials test the best way to detect certain diseases or health conditions. Quality of Life trials (or Supportive Care trials) explore ways to improve comfort and the equality of life for individuals with a chronic illness. Classification of Clinical Trials There are three types of clinical trials – phase I, phase II and phase III – each one is designed to learn something different about a new medical treatment. Phase I Trials A phase I trial is the first test of a new treatment, and it uses the fewest number of patients (20-30 patients is typical). A phase I trial for a new drug is designed to determine the safety of the new drug, how to best administer it and the correct dosage (i.e., one that will minimize undesirable side effects). Because investigators are very interested in how the drug behaves in the body, patients in a phase I trial undergo frequent monitoring of their vital signs. Although drugs being tested in a phase I trial have shown promise in the laboratory, there is no guarantee that the drug will have any positive effects on a patient. Patients participating in a phase I drug trial help advance basic medical knowledge; they may or may not reap any personal benefits. Phase II Trials After a phase I clinical trial has determined the safe dose of a drug, it can enter a phase II trial, which begins the process of determining the drug’s effectiveness in treating a specific type of disease. Because a phase II trial involves more patients than a phase I trial, physicians also have a chance to observe any less common side effects associated with the drug. In a phase II trial, which can involve 100 patients or more, physicians carefully monitor patients for a drug effect. For example, in a clinical trial testing a drug to increase the number of platelets in the blood, patients would have frequent blood samples taken, but they might also undergo several physical exams and other tests. The high level of patient monitoring in a phase II trial can be very time-consuming, so patients should take this into account when considering a phase II trial. If a drug in a phase II trial brings about a positive change in at least one-fifth of the patients, then it can be tested in a phase III trial. However, if the new drug has shown very positive effects in patients, the FDA also has the option of approving the drug for general use at this point. Phase III Trials A phase III trial involves the largest number of patients, typically several hundred, even thousands of patients. Phase III trials are randomized, which means that some of the patients in the trail are randomly chosen to receive the experimental treatment, while the others receive a standard treatment. The outcomes of the patients receiving the new treatment (the treatment group) are compared with the outcomes of the patients receiving the standard treatment (the control group). In some phase III trials (single-blind studies), patients do not know which control group they are in. In a double-blind study, the physicians also do not know which patients are in the treatment group and which are in the control group. Blinded studies are used to prevent biased study results. If a new drug successfully passes a phase III trial, the FDA will approve the drug for marketing to the general public.

Preparation and Standardization of 0.1 M Disodium Edetate (EDTA)

Preparation and Standardization of 0.1 M Disodium Edetate (EDTA) Preparation: · Take about 100 ml of water in a cleaned and dried 1000 ml volumetric flask. · Add about 37. 2 gm of Disodium edetate with continues stirring. · Add more about 700 ml of water mix. · Make up the volume 1000 ml with water. Mix solution thoroughly. · Keep the solution for atleast one hour and than carryout the standardization. Standardization: · Weigh accurately about 400 mg of Calcium Carbonate. · Previously dried at about 110°C for about 2 hour. · Transfer it in a cleaned and dried 500 ml conical flask and add about 10 ml of water with gentle stirring to form slurry. · Dissolve the carbonate in 2 ml of dilute hydrochloric acid and shake well until it dissolve. · Add 100 ml water through inner surface of the flask with the stirring of solution. · Add 30 ml of 0.1 M Disodium edetate (prepared) from the burette with constant stirring. · Add 15 ml of Sodium hydroxide solution with constant stirring. · Add 300 mg of hydroxy nephthol blue solution as a indicator. · Add 0.1 M Disodium edetate (Prepared) with constant stirring and titrate it until the solution gives blue colour. W x 1000 Molarity of 0.1 M Disodium edetate = ---------------------- BR x 100.09

Assay of Ascorbic acid

Assay of Ascorbic acid Reagents Required: 1.0M Sulfuric acid 0.05M Iodine Procedure Weigh accurately about 0.1gm of sample and dissolve in a mixture of 100 ml freshly boiled and cooled water and 25ml of 1M sulfuric acid. Immediately Titrate with 0.05M iodine, using starch solution as indicator until a persistent blue-violet color is obtained. Each ml of 0.05M iodine is equivalent to 0.008806gm of ascorbic acid. Calculation: BR X Actual molarity X 0.008806 X 100 % of Ascorbic acid = ---------------------------------------------------- 0.05 X Wt. Of sample BR= Burette Reading

Differece between water content and loss on drying (LOD) RAJA PATEL

Differece between water content and loss on drying (LOD)   RAJA PATEL

A lot of pharma professionals have the confusion regarding the concept of water contentand loss on drying. Both have considerable difference to understand.

Water content is determined by the Karl Fischer titration method and it consists of only water i.e moisture content. The results does not contain other volatile matter except the water.

Loss on drying (LOD) is determined by heating the sample bellow its melting point in an oven and it includes all volatile matter including water content and solvents.

Loss on Drying is an unspecific analytical technique removing not only water but all other volatile impurities like alcohol etc. from a sample.

The degree of drying is dependent on,

Temperature

Drying time

LOD or total moisture content of Pharmaceutical products can include both bound (e.g. water of hydration) & free water.

In cases there are additional traces of other volatile impurities present , like alcohol ; LOD may be higher than water content.

In other cases , LOD may be lower than water content, as bound crystal water may not be removed by heating.

% LOD = % Water content - % water molecule in the API

The Loss on Drying Test is designed to measure the amount of water and volatile matters in a sample when the sample is dried under specified conditions. e.g 105°C, 3 hours.

•The nature of the drug substance that is to be weighed and used in compounding a prescription must be known exactly. If the substance is a hydrate, its anhydrous equivalent weight may need to be calculated. On the other hand, if there is adsorbed moisture present that is either specified on a certificate of analysis or that is determined in the pharmacy immediately before the drug substance is used by the procedure under Loss on Drying, this information must be used when calculating the amount of drug substance that is to be weighed in order to determine the exact amount of anhydrous drug substance required.