What are differences between Reprocessing and Reworking?

Reprocessing	Reworking
The intermediate or API does not conform with standards or specification which back into the process and reprocessing by repeating a crystallization step or other appropriate chemical or physical manipulation steps that are part of the established manufacturing process	The intermediate or API does not conform to standards or specification which reworked with different process which does not part of the established manufacturing process.
Example: To achieve the desire particle size resifting the material with previous mesh size.	Example: To remove the impurities, different purification solvent used apart from the manufacturing process.

The reworked batch subjected for appropriate testing and stability testing prior to distribution. The quality comparison should required between original process batch and reworked batch. If required additional analytical method should be used for reworked batch testing. In case of reworked to be performed for single batch, then report to be made and batch shall be released after satisfactory data of stability and finished product quality. Additionally reworked manufacturing process should validate, in case of frequently occurrence.

Annual Product Quality Review (APQR / PQR)

Annual product quality review shall be evaluated and recorded, annually for specific drug substance or drug product to verifying the consistency of the manufacturing process.  

The APQR / PQR shall have minimum following content:

1. A review of key starting material quality and its vendor for product
2. A review of packaging materials quality and its vendor for product
3. A review of critical in-process control of API and its intermediate
4. A review of critical process parameters of API and its intermediate
5. A review of all batches that failed to meet established specifications
6. A review of quality attributes of all finished product batches
7. A review of all critical deviations
8. A review of OOS (Out-of-Specification) batches quality and related investigation
9. A review of product specific changes carried out in specification, system, manufacturing records, analytical method, validation etc
10. A review of stability results (annual and validation batches);
11. A review of all quality-related returns goods
12. A review of all, complaints and recalls
13. A review of adequacy of corrective actions and preventive actions taken for complaint, recall, return goods etc.

The results of this review are evaluated and assessment made of whether corrective action or any revalidation shall be taken for product. Reason for corrective action and documentation And actions are completed in a timely and effective manner.

Drying, Miling and Blending Validation

Brief about Drying, Miling and Blending Validation:

Drying, Milling and Blending validation shall be considered as part of Prospective Process Validation. This validation performed to evaluate the drying time, temperature, particle size distribution and homogeneity of the material within the batch.

Purpose: The purpose of this validation is defined as the process of combining several centrifuge loads from a single crystallization batch to drying, milling and blending to get the homogeneous final API batch of drug substance. The validation performed for Drying, Milling and Blending as defined operations in BMR for drug substance. Preferably, three prospective process validation batches (Exhibit batches) should be selected for validation.

Critical process parameters for Drying, Milling and Blending operation for API need to specify in protocol with process operation no., process operation description and standard requirements as define in BMR.

Defined the sampling plan for drying, milling and blending operation of API including with following details
 
Ø  Stage No and Name
Ø  BMR operation no.
Ø  Test parameters (sample to be tested)
Ø  Acceptance criteria for test parameters
Ø  Reference specification no. to be followed for validation
Ø  Sampling point / location (sample to be drawn from which location e.g reactor, centrifuge, dryer etc).
Ø  Sampling Interval (to be required in reaction monitoring, blending validation samples etc)
Ø  Sampling container (Sample to be collect in which container)
Ø  Approx qty. of sample (required qty. of sample for analysis).

Validation sample shall be labelled with necessary details such as Name of Product, B. No., Stage, Sampled Date, and sampled by, Sampling point / location etc
 

Blending Validation

The purpose of the blending validation

The purpose of blending is defined as the process of combining API of different batches within the same specification to produce a homogeneous API with large batch size. This validation is applicable only to mixing the different batches of same API to increase the batch size of drug substance. In-process mixing of fractions from single batch (e.g. collecting several centrifuge loads from a single crystallization batch) or combining fractions from several batches for further processing is considered to be part of the production process and it is not considered to be bending validation.

Blending validation shall be performed in following criteria

Ø  Blending of small batches to increase batch size.
Ø  Blending of tailings (i.e. relatively small quantities of isolated material) from batches of the same API
    to from a single batch.
Ø  Change in validated blending batch size.

Minimum three consecutive API batches shall be selected for blending validation.

Following parameters shall be similar in selected blending validation batches:

Ø  Batch Size of blend batch
Ø  Approved individual batches should released with similar specification
Ø  Equipment to be used for blending
Ø  Blending process e.g. RPM for blender
Ø  Blending time

Extensive analysis of blending validation batches shall be done for critical attributes (e.g. particle size distribution, bulk density and tap density and assay during the validation. After completion of bending validation, blending batches evaluated against the approved Finished product specification as per in-put batches.

Blending validation shall be considered as successful after satisfactory completion of six months stability data for Accelerated Condition (40° ± 2°C / 75% ± 5% RH) and Long Term Condition (25°C ± 2°C / 60% ± 5% RH) of selected batches.

Blending validation report shall be prepared after completion of three consecutive blending

Batches. In case, there is no requirement for three batches; interim blending validation report shall be prepared based on successfully completion of one or two batches. The final report shall be prepared when as completion of third batch. If changes in blending batch size, RPM and blending time then revalidation for blending shall be performed as per blending validation.

 

Queen of Angle School Exam and educational trip Post Pond

Dear Friends,

Due to heavy rainfall since last two days, eximination will be post pond further. Still school has not anounced officail declaration.

Also the Education trip which to be departure on 27.09.2013 from Queen of Angle will be postpond.

Famous School in Bharuch

 List of famous school for primary and higher secondary education in Bharuch

School Name	Syllabus	Address	Distance from Zadeshwar / Bharuch
Allied High School Bharuch		Nailesh park, Near Bharati Nagar Opp. J B Modi Park, link road Bharuch-392001	7 km
Delhi Public School	CBSE	Dahej, Bharuch-392130, Gujarat	25 km
Jawahar Navodaya Vidyalaya	CBSE	Roopnagar, Jagadia, Bharuch – 393110 Gujarat	25 km
Queen of Angels convent high school	CBSE ICSE	Vadadla, Bharuch	3 km
GNFC School	GSEB	GNFC Township, Narmadanagar, Bharuch, Bharuch, Gujarat	2 km
The Adithya Birla Public School	CBSE	Dahej, Bharuch...	30 km
Aditya International School	CBSE	Jagadia, Bharuch – 393110 Gujarat	25 km

Famous Places near by Bharuch

1. Kabir Vad - Shukal Tirth (12 km from Bharuch)
2. Kavi Kamboi (56 km from Bharuch)
3. Azva-Nimetha water park (100 km from Bharuch)
4. Snow water Park - Surat (70 km from Bharuch)
5. Snow water Park - Ahmedabad (210 km from Bharuch)
6. Swaminarayan Temple - Bharuch
7. Nilkanthshwar Mahadev Temple (3 km from Bharuch)
8. Golden Bridge (3 km from Bharuch). It is longest bridge on Narmada River
9. Sardar Sarovar (75 km from Bharuch) Bigest water dam on Narmada river
10 Sayajirao Gayakwad Palace - Vadodara (80 km from Bharuch)
11. Guman Dev Temple (Hanumanji Temple) - 10 km from Bharuch

 

Qualification of hollow sampler / thief sampler / sampling device

The objective of this protocol is to demonstrate the capability of Sampling Device for its intended application to deliver sampling and acceptable cleaning level.

CLEANING PROCEDURE FOR SAMPLING DEVICE FOR QUALIFICATION:

Prior to qualification, sampling device shall be cleaned as per procedure defined below

a)      Dismantle hollow pipes and end cap of the sampling device.

b)      Inspect all parts of sampling device for corrosion, if any.

c)      Flush all parts of sampling device with purified water till removal of any extraneous matter.

d)      Prepare 10% v/v Nitric Acid Solution (HNO₃) and kept the sampling device in Nitric Acid Solution for 8 hours

e)      Drain the acid solution and clean the device, inner and outside with sufficient qty of water.

f)       Collect the rinse samples of water and check the pH of water with pH meter (pH Limit - Between 6.0 and 7.0).

g)      If pH found within the limit, follow step no (i) and onwards.

h)      If pH not within the limit, follow steps (e) and (f) till the pH is found within the limit.  

i)        Inspect all parts of sampler, visually for removal of extraneous matter,

j)        Dry all parts of sampling device at room temperature or using hot air drier.

k)      Assemble the sampling device.      

Qualification:

Check the size and dimensions with calibrated measuring device e.g. measuring tap, scale etc and record. Check the smoothness of the surfaces. Check the MOC of sampling device against the certificate provided by vendor

Performance qualification:

Check the volume capacity by pouring the water in hollow sampling device and collect in empty beaker and weight.

Calculation formula for weight (A): weight of water x density of water

The observed weight shell be within the ± 15 % of theoretical capacity. Theoretical capacity shall be taken from vendor in cc or ml.

Cleaning Levels

Change over cleaning activity shall be separate in three different level based on their criticality. This approach is outlined in the below.

Level	Thoroughness cleaning	Cleaning Validation	Example
2	Carryover of previous product is critical.	Essential / Must	API A àAPI B
1	Carryover of the previous product is less critical	Necessary	Crude API A à Intermediate of API B
0	Carryover of the previous product is sequential earlier stage of API	Not required, only gross cleaning shall be done	Crude API à API A

Level 2 is indicating that cleaning validation is essential and must be performed for product changeover from API A (Previous Product / Product to be cleaned) to API B (Product to be taken / Next Product).

Level 1 is indicating that cleaning verification shall be performed for intermediates changeover.

Level 0 is indicating that gross cleaning shall be performed for sequential intermediates changeover of API.  

Cleaning Validation Calculation formula for Target limit for swab samples and Rinse Samples

Target limit for Swab samples for individual equipment:
Based on the MAR, target limit for swab sample to determine based on the following calculation:

                                       A x 1000 x B x RF                                                       

Target value for swab (in ppm) = -----------------------------
                                                                   C x D

Where,
A = MAR in mg of “previous” product or “Product to be cleaned”
B = Swab sample area (in 100 cm²)
RF = Recovery factor for Glass, SS or other MOC of equipment
C = Total contact surface area of equipment (in cm²)
D = Dilution volume of swab sample, 1000 = Conversation factor from mg to ppm


Target limit for Rinse sample for individual equipments:
Based on the MAR, target limit for Rinse sample to determine based on the following calculation:

                                                      MAR in mg                                                      

Target Rinse (in ppm) = ------------------------------------------------------------------------ x 1000
                                          Total Volume (L) of final Rinse for train of equipments