What is the difference between them? Topics related to Pharmaceutical Production, Quality Assurance, Quality Control, Regulatory Affairs, Engineering, Microbiology, Formulations, R&D, GMPs, Regulations, Inspections

What is the difference between a strip pack and a blister pack?

The difference between a strip pack and a blister pack is that a strip pack doesn’t have thermoformed or cold formed cavities; the strip pack is formed around the tablet or capsule when it is dropped to the sealing area between sealing moulds. Blister packing contain PVC/PVDC foil in one side and   Aluminum foil in the other side, whereas in Strip packs contains aluminum foil in both sides. Advantage: The Al/PE laminated film has the same protective property as cold forming aluminum film, that perfectly protects the medicine from moisture, light and oxygen. Disadvantages: Slower speed of production compared to thermoforming blister pack; Because it doesn’t have pre-formed cavities, the packaging area for each item is larger than the blister pack.

What is the difference between Calibration and Validation?

Calibration is the demonstration that, a particular instrument or device produces results within specified limits by comparisons with those produced by a reference or traceable standard over an appropriate range of measurements. Whereas Validation is a documented program that provides high degree of assurance that a specific process, method or system consistently produces a result meeting pre-determined acceptance criteria. In calibration performance of an instrument or device is comparing against a reference standard. But in validation such reference standard is not using. Calibration ensures that instrument or measuring devices producing accurate results. Whereas validation demonstrates that a process, equipment, method or system produces consistent results (in other words, it ensures that uniforms batches are produced).

What is the difference between Disintegration and Dissolution?

Disintegration is a disaggregation process, in which an oral dosage form falls apart in to smaller aggregates (Disintegration time is the ‘break up’ time of a solid dosage form). Whereas dissolution is a process by which solid substance enters in the solvent to yield a solution. It is controlled by the affinity between the solid substance and the solvent. In other word disintegration is a subset of dissolution.

What is the difference between FDA Form 482 and 484?

FDA Form 482 – Notice of Inspection Form 482 is an official notice of FDA inspection. This document gives FDA the authority to enter a facility and inspect as per section 704 of the FD&C act. FDA Form 484 – Receipt for Samples Form 484 is an acknowledgement of samples received by FDA as per section 704 of the FD&C act.

Form 483 and Warning Letter’s are two serious documents issued by USFDA which are very different in regulatory and legal prospective. “FDA 483 lists observations made by the FDA representative during the inspection of a facility. They are inspectional observations, and do not represent a final Agency determination regarding firms compliance.” The FDA-483 can be amended after an inspection by the investigator who issued it and re-issued.   The Warning Letter is a document that usually originates from the FDA-483 observations that have been linked to citations by one or more legal reviews within the Compliance and legal branch of the FDA. A Warning Letter is informal and advisory. It communicates the agency's position on a matter, but it does not commit FDA to taking enforcement action. For these reasons, FDA does not consider Warning Letters to be final agency action on which it can be sued. The Warning Letter is issued by the agency and not the investigator. FDA 483’s Warning Letter The Form 483 is issued for inspectional observations. It lists the alleged deficiencies or issues of non-compliance in the manufacturer’s quality system. Warning letters are issued for violations of “regulatory significance” (Significant violations are those violations that may lead to enforcement action if not promptly and adequately corrected). The Form 483 is issued by the inspection team alone. The warning letter is issued from a higher level FDA official or officials.  Bad inspections lead to Form 483s. Warning letters usually result from multiple lacking responses to issued 483s, or other issues much more serious that require quick attention/escalation.

What is the difference between Hard Gelatin and Soft Gelatin Capsules?

Both the hard and softgel capsules are made of gelatin.Thus the difference between these two types of capsules lies in the design and manufacturing technology which are detailed below. Hard Gelatin Capsule Soft Gelatin Capsule Made of hard gelatin Made of soft gelatin Produced in two halves consisting of a body and cap Produced as a single piece of gelatin, rather than two halves attached Mainly used for filling dry and powdered content Mainly used for oil-based formulations They’re manufactured using different machines, for shell production and encapsulation. A different process is employed in manufacturing Manufacturing and filling is done using the same machine, as part of a single process Hard gel capsules usually are cylindrical Can be made in a variety of shapes such as the oval, round, tube-like, fish-like, etc. These are made of only hard gelatin, colorings, plasticizer and titanium dioxide Lots of ingredients are used, i.e. soft gelatin, plasticizer, sugars, preservatives, colorings, opacifier, etc. The ratio of gelatin and plasticizer is 1:0.4 The ratio of gelatin to plasticizer is 1:0.8 Available in a range of sizes Size variety is limited

What is the difference between Humidity and Relative Humidity?

"Humidity" and "Relative Humidity" is not the same thing. Humidity means amount of water vapour present in air with respect to total amount of air. Relative Humidity is the amount of moisture in the air 'relative' to the temperature (i.e relative humidity is the amount of moisture in the air compared to what the air can "hold" at that temperature. When the air can't "hold" all the moisture, then it condenses as dew). The relative humidity is a measure of the amount of water vapor in the air (at a specific temperature) compared to the maximum amount of water vapor air could hold at that temperature, and is given as a percentage value. Relative humidity depends on the temperature of the air.

What is the difference between KF and LOD?

In pharmaceuticals, several methods are employed to determine the water content of a substance/product. Among which Karl Fischer Titration (KF) and Loss on Drying (LOD) are most honored and largely reliable methods. Loss-on-Drying (Weight Loss) This method uses the principle of drying a sample of the product and comparing the weight before and after drying. The difference in weight represents the moisture that is in the product. This can be accomplished by using various manner such as drying ovens, infrared balances, and infrared lamps. Whatsoever, the drying conditions are strictly specified. The difference in weight after drying is due to the loss of all evaporated matter, which is taken to represent the moisture content. Repeatability and accuracy of this method solely depend up on the temperature and time controls adopted during testing. The difficulty is that this technique measures all the moisture lost from the sample, which includes not just water but also any other volatile component already present in the sample (like residual volatile solvents) or created by polymerization or degradation of the sample. Karl Fischer (KF) Titration Karl Fischer titration is a very specific determination method which detects and measures only water, including water of crystallization and surface-absorbed water. It is based upon a redox reaction involving water and iodine in the presence of a base, an alcohol, and sulfur dioxide. The water-iodine reaction is dependent upon the presence of water, and therefore the titer of reagent used up in the reaction reflects the amount of water in the sample as there is no other source of water. The KF reagent contains iodine and when it has completely reacted with the total water, excess iodine appears in the solution, causing a color change as well as an electrometric change which can be detected by a double platinum electrode. KF titration measures total water and is not affected by the presence of residual volatile solvents. It has a wide and sensitive range of determination from a water content of 100% to 1 ppm. KF LOD KF is a method, which measures only the water content (i.e. it's water-specific) in a product sample. LOD on the other hand, measures the total change in weight of a material as a result of drying. For some products, components such as alcohol or fat evaporate with the water. Therefore, the LOD method measures both the water and volatile impurities such as those mentioned previously Karl Fischer titration is a chemical method. It involves adding a reagent to the sample to cause a reaction that converts the water in a product to a non-conductive chemical. Loss on Drying compares the weight of a product before and after it is dried. This difference in weight is taken as the percentage of moisture in the product.

What is the difference between mg and IU?

Basically Mg is mass......... IU is effect Milligrams (mg) are a measure of mass(weight). A milligram is one thousandth of a gram. International Units (IU) are a measure based on the biological activity of a substance in the body. These units are arbitrarily set by a committee of researchers commissioned by the World Health Organization. The goal is to provide a measure of the effect on the body a substance will have regardless of its mass. For Ex: 1 IU of Vitamin C is 50 mgs, but 1 IU of insulin is .045 milligrams. That's for the pure crystalline versions of those chemicals: a different preparation or a related chemical may have the same effect using a different amount, and that would also be 1 IU. IU is used for vitamins, hormones, some drugs, vaccines, blood products and similar biologically active substances. Despite its name, the IU is not part of the International System of Units used in physics and chemistry.

What is the difference between Thermoforming and Cold forming Technology in Blister packing?

Thermoforming is a technique that involves heating sheets of PVC prior to insertion into a blister machine. This is typically achieved by passing the sheets between upper and lower heating plates. When a sheet enters a thermoforming blister machine, it is soft and pliable and can be forced to take on the shape of a mold through the application of pressure. In some cases, a mechanical stamp will be used in addition to the application of pressure, particularly when the shape of the mold is difficult or complex. Cold forming is a technique that does not involve any application of heat. Unlike the thermoforming method that uses clear PVC, this technique uses thin sheets of laminate film that contain aluminum. In order to create packaging out of these sheets, a blister machine will typically use a stamp to force it into a form. The aluminum-based film will tend to stretch and retain the shape after the stamp has been removed. This type of blister pack is typically used to contain pharmaceuticals, since the aluminum-based film tends to prevent moisture from entering the packaging.

What is the difference between Warning Letter and Untitled Letter?

If a person or firm violates the Federal Food, Drug and Cosmetic Act (FD&C Act), FDA may give them an opportunity to take voluntary and prompt action to correct the violation before FDA initiates an enforcement action. FDA will issue either a Warning Letter or an Untitled Letter, depending upon the nature of the violation. FDA uses Warning Letters for violations that may lead to enforcement action if they are not promptly and adequately corrected. FDA uses Untitled Letters for violations that are not as significant as those that trigger warning letters. Unlike a Warning Letter, an Untitled Letter does not include a statement warning that failure to promptly correct a violation may result in an enforcement action. An Untitled Letter cites violations that do not meet the threshold of regulatory significance for a Warning Letter. An Untitled Letter differs from FDA warning letter in following aspects. The letter is not titled    The letter does not include a statement that FDA will advise other federal agencies of the issuance of the letter so that they may take this information into account when considering the awarding of contracts. The letter does not include a warning statement that failure to take prompt correction may result in enforcement action. The letter does not evoke a mandated district follow-up. The letter requests (rather than requires) a written response from the firm within a reasonable amount of time (e.g., "Please respond within 30 days"), unless more specific instructions are provided in a relevant Compliance Program. Any appropriate agency compliance official may issue an Untitled letter. Warning Letter VS Untitled Letter Warning Letter Untitled Letter Does not represent official FDA enforcement action Does not represent official FDA enforcement action Includes statement about potential enforcement action Does not include statement about potential enforcement action Intended to induce voluntary compliance with regulations Intended to induce voluntary compliance with regulations Is the most serious communication before the FDA takes enforcement action Less serious than warning letter (still serious!)

What is the difference between ALCOA and ALCOA Plus?

ALCOA and ALCOA Plus are acronyms related to data integrity. When the concept of Data integrity was first introduced in late 90’s, regulatory agencies used the term ALCOA to indicate the main 5 principles of data integrity, which are referring to Attributable, Legible, Contemporaneous, Original and Accurate. Later on the concept of ALCOA Plus introduced to the industry indicating the 5 main principles of data integrity (i.e Attributable, Legible, Contemporaneous, Original and Accurate) plus additional emphasis on the attributes of being complete, consistent, enduring and available.

What is the difference between Contamination and Cross Contamination?

Contamination is the undesired introduction of impurities (of chemical and microbiological nature) or foreign matter, into or onto a starting material or intermediate, API or finished product during: storage, sampling, processing, packing or transport. Whereas Cross contamination is the contamination of a starting material, Intermediate or finished product with another starting material, intermediate or product. Reason for contamination/cross contamination of drug substance/product can vary and caused by multiple factors. Facility constraints, lack of procedures, lack of awareness etc. are the few among them.

What is the difference between Reference Listed Drug (RLD) and Reference Standard (RS) in Orange Book?

Reference Listed Drug (RLD): An RLD is the specific listed drug on which an ANDA applicant relies in seeking approval for its ANDA. Reference Standard (RS): A reference standard (RS) is a listed drug selected by FDA that an ANDA applicant must use in conducting an In-vivo bio equivalence study.

What is the difference between GDUFA and PDUFA?

Both GDUFA and PDUFA are US FDA’s User Fee programs, which help FDA to hire and retain sufficient numbers and types of technical and scientific experts to efficiently conduct reviews of human drug applications (NDA and ANDA) and improving the predictability of review processes GDUFA is related to ANDAs whereas PDUFA is related to NDAs.  GDUFA: Generic Drug User Fee Amendments. The Generic Drug User Fee Act is a law designed to speed access to safe and effective generic drugs to the public, and reduce costs to industry. PDUFA: Prescription Drug User Fee Act  is  a law passed by the United States Congress in 1992 which allowed the Food and Drug Administration (FDA) to collect fees from drug manufacturers to fund the new drug approval process.

What is the difference between Biologics and Bio similar ?

Biologics or biological products are medicines made from living organisms through highly complex manufacturing processes and must be handled and administered under carefully monitored conditions.  Biologic: A biological product or biologic, is a preparation, such as a therapeutic drug, monoclonal antibodies or vaccines, that is made from living organisms (such as microorganisms, animal cell or plant cell). Compared with conventional chemical drugs, biologics are relatively large and complex molecules. They may be composed of proteins (and or their constituent amino acids), carbohydrates (such as sugars), nucleic acids (such as DNA), or combinations of these substances. Patients receives biologics by injection under skin (subcutaneously) or by intravenous infusion and cannot take them orally, since the digestive process break down the biologic and make them ineffective. Bio similar: A Bio similar is similar but not identical to a brand name biologic medicine (reference product). Bio similar has the same mechanism of action, route of administration, dosage form, and strengths as the brand name biologic medicine (reference product). Bio similar is highly similar, but not structurally identical and exact replicas of the brand-name biologic; there can be minor differences in clinically inactive components. Because biologics are more complex than chemical drugs, both in composition and method of manufacture. Since bio similars are not identical, they are not generic versions of the biologic they are copying, but they are affordable alternatives that work similarly and are shown in studies to have equivalent outcomes.